A Q&A with MitoQ’s co-creators

It’s not everyday a company turns 10! For MitoQ’s 10th birthday – we wanted to celebrate. We were thrilled to be able to do this in the company of the MitoQ molecule’s co-creators Professors Mike Murphy and Robin Smith. The pair joined us for a party at MitoQ’s headquarters in Auckland, New Zealand and were also generous enough to sit down for a Q&A interview with our Head of Brand and Communications Liz Hancock.

To learn about why Mike and Rob are pioneers in their fields, what led to the creation of MitoQ, how they look after their mitochondrial health – and more – watch the video below or keep reading.

Liz Hancock

Hi, I am Liz from MitoQ, and we've got two super special guests here today that we're excited to meet, and we're excited to introduce you guys to them as well. We have Professor Mike Murphy and Professor Robin Smith. They are the co-creators of mitoquinone mesylate, the hero ingredient in MitoQ. And this is the first time they have been to our offices and the first time a lot of the team have met them.

So I'm going to introduce them to you guys first by getting them to tell us a little bit about their backgrounds.

Mike Murphy

Hi I am Mike Murphy. I did undergraduates in chemistry in Trinity College Dublin, followed up by a Ph.D. in biochemistry in Cambridge. And then, after that, I started working on mitochondria for the rest of my career. After that, I moved after a few years to the University of Otago, the biochemistry department in Dunedin, New Zealand. And, while there, I was working on aspects of targeting mitochondria - and it was there that I started working with Rob Smith on designing molecules to target them to mitochondria.

Rob Smith

And I'm Rob Smith. I'm an organic chemist. My interest is designing new ways to make molecules and making molecules, which some people may find interesting. So I was an undergraduate and graduate at University of Otago and after some time in the States, came back to a faculty position at Otago and I was relatively established as an organic chemist in Dunedin.

And then this young Murphy arrived in the biochemistry department and came over to talk to me very, very aggressively about mitochondria and how that was the only thing you should be talking about! So, I quickly went and read up about mitochondria and came back and then Mike came up with some ideas of making some chemicals to go into mitochondria.

And, more importantly, in the first summer I think he was there, he came to my chemistry lab and sat down there for a week or two and tried to make one of the chemicals himself. After that I decided it would be better if we had real chemistry and that's the way we got together. And we've collaborated on and off for over 20 years and we're still talking to each other!

Liz

Which is great. But yeah, we all share that passion for mitochondria as well. I think, you know, the second you understand a little bit about them, you know, it's just something you don't stop gaining an interest in it. So, why did you guys create Mitoquinonel Mesylate? Like what was the sort of problem you were trying to solve? Because now it's known as a pioneering cell health molecule. But back then there was nothing that could do what it could do.

Mike

At the time, we were trying to get small molecules to go into mitochondria and we used this idea of the small, positively charged molecules can go through membranes to bring things into mitochondria. And that led onto the idea that we could have antioxidants to protect mitochondria. And with that we made MitoQ, which turned out to be a very effective molecule.

Rob

Yeah. So the basic molecule Mike wanted to make was a molecule where we had the positive charged species and chemically weld it to something else, which was known to be a bio reactive molecule such as an antioxidant. So, my challenge was to just hook these two pieces together. You had a sort of a truck and a trailer type idea, and one of the very first molecules we made, simply because it was chemically easy to get, were the MitoQ series.

And in that series, one of the very first we made was one where the separation between the two dumbbell parts was appropriate to get into cells and do all sorts of fancy antioxidant properties. Later on, when we decided the first one was quite effective, we made other chemicals, the same two components, but closer together or further apart, and these weren’t anywhere near as efficient.

So, we’d like to say it was logical science, but on top of that, it was good luck that the first one we made was in fact very effective, biologically.

Liz

And so just coming back to something you said earlier, why is it important for antioxidants to get into mitochondria?

Mike

Well, we know that mitochondria are the heart of metabolism inside the cell and, as part of their function, they end up producing - as a side product - a lot of free radicals, which can cause damage. And this causes what's called oxidative damage, which contributes to aging and to general cell stress. So, for that reason, antioxidants are often used as a way of trying to counteract free radicals because they grab the free radicals and stop them from causing damage and stress to the cell.

Of course, most antioxidants like vitamin E or CoQ10 or vitamin C do work reasonably well, but it's hard to increase the amounts inside the cell. And they're not concentrating inside mitochondria. Because mitochondria are the major source of free radicals inside the cell, we thought if we made an antioxidant that went in and accumulated inside mitochondria, that might be a good location to mop up the free radicals at the center of the cell where they're being produced.

So that was kind of the rationale for making a mitochondria targeted antioxidant, such as MitoQ.

Liz

Can you tell us a little bit more about how MitoQ actually works?

Rob

The reason it works is, first of all, you've got to get inside mitochondria - and mitochondria, like anything in a cellular system, have natural protection systems, so it has to slide through a cell wall and then it has to go through the outer membrane of a mitochondria. And what we could do was exploit the fact that there is a potential across the mitochondrial wall.

And if we had the molecules engineered chemically, properly, they would slip through that mitochondrial wall, basically driven by the potential across the cell wall. So we had to make molecules which were not very water soluble because they wouldn't go through the cell wall - not very long and sticky and greasy because they would just stick to anything they met and not go through the cell wall.

We had to find that intermediate space. And, as I said previously, we were fortunate. One of the very first ones we made was one that turned out to be one of the biggest going through the cell wall effectively.

Liz

And so what are the benefits of having an antioxidant that can get into the mitochondria?

Mike

I think it comes back to the idea that we think that free radical production in mitochondria can contribute to cell stress and can respond to all sorts of things such as personal stress, overwork, tiredness, things like that. But we think that these can be contributing to those factors. So the notion would be that these factors will increase, especially as we get older/ progress in life.

And so if MitoQ is there, it can dampen down some of this damage and maybe enhance the way our cells are able to function and cope with the stress. So that's the notion that we feel - that by loading up the mitochondria with some protective molecules - you have a better chance of cells not being so stressed or damaged by the things that they are exposed to during life.

Liz

And we talk a lot about how the human body is made almost entirely of cells. So, you want those to be working properly, don't you? You don't want anything to be compromising their health, such as mitochondrial damage.

Mike

Yes. You're made of cells. The cells contain mitochondria. The mitochondria are essential for cells to be happy and healthy. And so it makes sense that if you can decrease some of the damaging events occurring in mitochondria, the cells should be able to function better.

Liz

And so, why would you need something like MitoQ? Can your cells get the antioxidants that you need from diet alone?

Mike

Diet is obviously very important and we're getting a lot of important nutrients and vitamins and antioxidants from our diet. So that's certainly a key aspect of healthy living. Many of the natural products that we have as antioxidants - or vitamins like vitamin E, vitamin C - they're vital for our bodies to keep them healthy and protect against some of these free radicals.

You can't get too many of those into mitochondria because the levels are closely regulated. So something that MitoQ can give you a top up of the antioxidant defenses on top of those other things that you'll be getting from your diet. However, it's obviously essential to eat well and have a proper diet. And then the idea would be that things like MitoQ, you may be able to add to the protection that you're getting, particularly as you get older and the absorption and distribution of some of these natural products in your body is maybe not so effective.

Liz

Yeah. I was going to ask you that - are those levels declining as you age?

Mike

Probably. We know that mitochondrial function declines as we age and we have a lot of damage to cells, inflammation, senescence, things like that - as we get older. A lot of this is probably affected by decreased mitochondrial function and, hopefully, by enhancing the protection, we can protect the mitochondria from some of these issues.

Liz

So I know that CoQ10 was this sort of starting point or the genesis point for MitoQ that you then went on and advanced it, improved it and helped it to get into the mitochondria. What is the difference between MitoQ and CoQ10, if you were going to sum it up quite succinctly?

Rob

Well, I think both CoQ10 and MitoQ have what I call the warhead, the very part that reacts with reactive oxygen species, these radical species, everybody knows about the cause, oxidative damage. The rest of CoQ10 is really greasy long chain. What we have done is taken off that chain, if you like, added a small chain, not greasy enough, and then added this other component - this phosphorus component, which carries the active warhead of CoQ10 into the mitochondria. And we have all the activity, the antioxidant activity that CoQ10 has, but we've now delivered it inside the mitochondria, which doesn't happen with CoQ10.

Mike

And another important thing to remember with CoQ10, as Rob says, it's incredibly sticky, greasy, so it's not going to be able to be transported very well inside our bodies. It's not actually a vitamin. It's actually made within our mitochondria and the amount that we make is closely regulated. So it's made to be used inside mitochondria and you can't increase the amounts of it there.

It also means we have no way of taking it up from our diet. The very small amount we can take from our diet is kind of accidental. It'll slip through a little bit but, because it's so sticky, it's very hard to get it into mitochondria. So it's not designed to get taken up into mitochondria. So that's part of the reason why we use the targeted version that has many of the advantages of CoQ10, but we can get far more into mitochondria to be protective.

Liz

So the two of you co-created MitoQ back in the 1990s - but MitoQ itself as a company began ten years ago. And so it's our 10th anniversary this year! I'm curious to know how you've seen the world's approach to mitochondria change in that time period, because I believe there wasn't really, you know, a wide understanding of the role of mitochondria and the importance of them when we're looking at health and kind of, I guess, quality of life.

Mike

So when rob and I started, there was a lot of interest in mitochondria from energy production that was thought to be the main role for mitochondria. Since then, we've seen the role of mitochondria expand dramatically in regulating cell function, in cell signaling and controlling things like inflammation, cell senescence, stem cell origins and maintenance.

So all this seems to be a key aspect of mitochondrial function that we understand. And so working in mitochondria for all my career, we've seen a huge renaissance in mitochondrial studies expanding to many areas of biology now. What Rob and I were doing was really at the outset of trying to target molecules to mitochondria so you could actually get protective molecules into mitochondria.

That's been used now by us, by many others to try and both protect mitochondria, but also as probes to try and understand what's happening inside mitochondria. So I think that was interesting to be there at the outset of what was happening.

Rob

Yeah. And if we go back to core chemistry, I think what we did was simply weld these two components together. But the idea of adding this positive phosphorus onto something that's bioactive, we maybe would unwittingly be the first to do that and publish it. And now in the chemistry world, many, many molecules, new molecules are made and all - if people are interested in what's the biology of that - almost inevitably they will hook up this positive phosphorus piece to try and get them into cells and into mitochondria.

As a result, I think our original paper that we published in a medium level journal gets quoted many, many times as the justification for hooking on this positive phosphorus. So by good luck or good management - you can argue which way - I think it has just set a scene now which has been taken up by hard-nosed chemists as well as interesting biologists too, and people like that.

Liz

Yeah. And you know, I guess it's a blessing and a curse to be pioneers, you know, kind of waiting for the rest of the industry to catch up in some way.

Mike

Well, it's always interesting to see this. Certainly, in the early days, you'd have things like, well, we're going to target molecules to mitochondria by using this chemical trick of tying it to a phosphonium. It was funny and often the referees would have many questions about, well, would that work? Is that going to work? This hasn't been proven. And, of course, then it went straight from that a year or two later to everyone knows this is the standard way to do it. It's not novel. Everyone can do it. So you don't get an intermediate time where they appreciate what you've done. But that's life.

Liz

Do you ever have moments where people are kind of telling you that this is possible and you have a sort of reality take moment where you're like, yeah, we actually created that. We made that that discovery?

Mike

You know, I have had one or two situations where a young student asked a question after a talk, and I was talking about a different subject and they said, well, have you thought about targeting this this group here to mitochondria using a phosphonium? And so, there was a bit of laughter in the audience, you know, so the student wasn't aware of the background. I said, “well, maybe that's a good idea.”

Rob

But I think one of the other points about this uniqueness of the phosphonium part is nobody had ever made a phosphonium salt - and, in the end, they put it into a human being. So we had to be aware that this potentially could be a toxic molecule inside. We could do animal studies, but eventually you get to humans and - all the cell studies, the animal studies are very nice and important - but at the end of the day you're asking a live, real human being to put something in their mouth and see how they react to it. In the early days, I think we discovered that for whatever reason, Mother Nature hasn't worked out how to destroy or get annoyed by having a phosphonium in a human body. And that's been a success. That's why MitoQ can be taken in humans. So that was something that we honestly never knew until we actually built up the knowledge and did it.

Mike

And I think that idea of moving it from the lab based thing into the humans, we have to give credit to Ken Taylor, who was the first CEO of what was then known as Antipodean and then became MitoQ, so he was a huge driver from his experience in the industry to actually get it developed and get it into a formulation that was actually going into humans.

So without Ken's wisdom and knowledge in these areas, it would have been very difficult for us to make that leap into making it available for humans.

Liz

Yeah, and that brings me on to my next question brilliantly, which is: it started with your first human study - was that at the University of Otago?

Mike

The first human study was a Parkinson's trial, and that was run by Barry Snow from the University of Auckland, who's a neurologist. And so that was the first big human trial that was run.

Liz

So, from that first human trial, you know, over the last decade that MitoQ has been around, it's exploded into over 700 studies on MitoQ, 18 clinical trials, and there are about 40 other clinical trials, all independent, all being run around the world about this amazing molecule and its potential. And, you know, there are new discoveries every week, every month about, you know, what it could potentially do. How does that compare to the vision you had for it when you first created it?

Mike

I don't think we had a vision. We were still trying and moving forward bit by bit. What is always very gratifying as a scientist is of course, that whatever you do in your lab gets repeated and either vindicated or shown to be incorrect by other people independently. So the fact that we've got independent studies, peer reviewed studies - over 700 around the world - and also independent clinical trials that are totally separate from us where people are just, they don't care whether MitoQ works, what they just want to find out is what it does.

That's been very interesting seeing something like that.

Rob

And as I said, back to my idea, there's this logic and a serendipity in all of this. If we hadn't made the original MitoQ, we could have made other variants, chemical variants, early on and they would have not done the job and we would have given up on them.

The other serendipity is, I had known Ken Taylor, who Mike just mentioned, from when he was a student the same time as I, and he just came around talking to me. He was looking for interesting science that may be commercialized. And I just mentioned to Ken several people he should talk to, a New Zealand scientist that maybe had something in their back pocket.

And I said, “Oh, by the way, there’s this mitochondrial maniac in biochemistry and we made these things and they seemed to be quite interesting and the university has taken some patent position on them.” And Ken said, oh yes, that's quite interesting - and we heard nothing. But almost at the 11th hour Ken came back and said I think we will set up and have a serious look at this MitoQ thing.

But just because he happened to know me from a million years ago when he was a wild student, allowed us to get it going in the commercial sense.

Liz

So, as we've discussed, mitochondria as a topic within health just seems to be growing and growing every year. I think it's, you know, yet to tip over into the greater public knowledge in the way that things like probiotics have. But you know, we feel that it is growing and it is building and it is something that eventually will become a very common way of managing your health.

Where do you guys sort of see mitochondrial health kind of exploding in the wellness industry?

Mike

Well, I've been working directly in the mitochondrial field since I did my PhD, so, you know, almost 40 years now. And over that time, the centrality of mitochondria in all aspects of health has become more and more evident, especially now in the idea of how to look after yourself with supplements, with exercise, with lifestyle as you take control of your own health.

Mitochondria are an aspect of that because how we affect ourselves with things like dietary restriction, intermittent fasting, good diets, all those things are probably impacting on our central metabolism, which is through mitochondria. In addition, the work we do now is not directly related to things like MitoQ, but in my lab it's relating to some other pathologies in which mitochondria are central.

So, for example, I have a strong interest in understanding the role of mitochondria, things like heart attack and stroke, which is making other compounds, some drugs that are targeted to those processes - and then mitochondria turning up and all sorts of things like cell senescence, neurodegeneration also in things like how stem cells operate. So, all these areas and inflammation is another big area of mitochondria.

So these surprising areas of mitochondria turning up now are quite intriguing and interesting to observe.

Liz

Am I the only one who kind of thinks about them as little aliens that control our bodies? I mean, they are quite phenomenal.

Mike

Yes. As you’re probably aware, mitochondria, if you look at a picture of a cell with mitochondria, the mitochondria look like little bacteria. And so in a cell there might be several hundred mitochondria - like little bacteria scattered through the cell. And of course that was their origin. Originally, about 3 billion years ago or so, they were separate bacteria which came to live inside our precursors of our cells.

And since that, there's been kind of a symbiosis, an arrangement between the mitochondria that do a lot of the hard work for the cell, provide energy, and in return the cell is protecting them. So many of us could see our cells are just ways of the mitochondria protecting themselves and our bodies are just ways of getting the cells around.

So a lot of interest in the various roles of mitochondria and how they originated within ourselves.

Liz

Well, on that note, what is the most interesting or fascinating thing that you've discovered about mitochondria in your careers?

Mike

There's so many interesting things that it's hard to know for sure, but some of the weirder things that we've found out about mitochondria are that they can actually be releasing signals controlling what's happening in the cell and even outside the cell. Some of our recent work, we found that mitochondria metabolism could be shifted in ways that they would send a signal to the rest of the cell.

And then, under some circumstances, the mitochondrial metabolism sent a signal outside the cell to surrounding cells. So very intriguing - from the idea that mitochondria were just a little engine on its own - to now that the mitochondria are sending out signals and feedback and controlling what's going on all around. So it’s been very intriguing finding that we've been working on the last few years now.

Liz

What do you personally both do on a daily basis to look after your mitochondria?

Rob

Well, I am quite young of course. But I think it's regular diet and a bit of exercise and, I think, just a healthy lifestyle. I don't have a mitochondrial-specific regime or anything like that. And I have taken MitoQ on occasions. But no, I'm not in regular use. My wife, bless her heart, does, but that's just loyalty to me, I think, more than anything else.

Mike

So, I think trying to understand metabolism from the perspective of mitochondria and how we eat: for example, I don't eat breakfast and I usually don't eat lunch - so I can get by with just one big meal a day. So, this idea of intermittent fasting, which is reprograming some aspects of metabolism in your mitochondria and also allowing you to clear debris which accumulates in your cells from oxidative damage to mitochondria. I'm trying to exercise pretty regularly, which is very important - so that your mitochondria are actually doing things all the time and you're turning over and keeping yourself active. Hugely important, I think. So those things, if you think about how they're operating, I think that makes a lot of sense to interpret what's going on.

Liz

And we've seen you doing your wild swimming in the Cam back in Cambridge and your cycling around Cambridge, and I believe you're over here visiting New Zealand at the moment doing a fishing holiday and I believe you were both cycling last week together!

Rob

Yes, well, I was cycling. Michael was well behind!

Mike

A long way behind! Yes, it was good. We did the Routeburn track with some American friends - with a combined age of over 240 - so we managed to make it without any casualties. And I've been fishing for the last couple of weeks. I'm now giving some lectures around New Zealand.

Liz

Fantastic. So, one final question to you, Mike. What is the role of mitochondria with regards to adrenal function?

Mike

So the adrenal function, these are the adrenal glands which are found just above your kidneys. These are very important glands in producing stress hormones like cortisol. And it turns out that mitochondria are actually the site within those where these molecules, like the stress hormones, are made on the surface of mitochondria. In addition to that central role in the metabolism of some of these stress hormones, we think that stress hormones like cortisol and things, that their production is related to cell stress in general terms around the body.

And there's feedback to that. So it's a very intriguing link between mitochondrial stress, mitochondrial function and these stress hormones and whether this feedback can be impacted by keeping the mitochondria healthy is an area that is very interesting to explore.

Liz

Fascinating. Well, thank you both so much for coming to visit us and for giving us some time to talk about the amazing creation of MitoQ and the amazing science that went into it. We're really honored to meet you both.

Rob

Thank you for talking to us.

Mike

Thank you.

Shop now