“Is Mitochondrial Respiration a Limiting Factor of Oxidative Metabolism” A Symposium Reflection

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“Is Mitochondrial Respiration a Limiting Factor of Oxidative Metabolism” A Symposium Reflection

Jorge Granados, M.S. |  Nov. 8, 2018

This is part ten of a series of blogs from attendees at ACSM's Conference on Integrative Physiology of Exercise. The following blog is a reflection on the debate titled “Is Mitochondrial Respiration a Limiting Factor of Oxidative Metabolism.”

It is 3:00 P.M. on Saturday; the weather in San Diego is gorgeous; the Aggie football game starts in an hour, but this is one of the last sessions of the IPE conference and something tells me that I should stick around for it. Although many attendees have flights to catch, vacations to begin, or football games to watch, I wasn’t surprised to see that the symposium was well attended. After all, every symposium and debate held during this conference has exceeded my expectations! That being said, I am grateful that I stuck around for this last session! Here is why:

The session was chaired by L. Bruce Gladden, Ph.D., FACSM, of Auburn University and Dr. Michael C. Hogan, Ph.D., FACSM of the University of California, San Diego.

Although mitochondrial respiration is not my area of expertise, Dr. Gladden delivered a great introduction explaining the limiting factors (e.g., pulmonary limitation, matching O2 delivery to utilization, O2 diffusion, mitochondrial volume, etc.) to oxidative phosphorylation/metabolism. He then noted that in order to better comprehend the many other controlling/limiting factors responsible for oxidative metabolism, we need to utilize diverse tools to assess different subject populations, exercise/contraction type and sample/analysis size. This set the scene for the first presenter of the symposium, Bruno Grassi, M.D., Ph.D., FACSM, (University of Udine, Italy) who discussed different tools of functional evaluation of oxidative metabolism.

Side note: During Dr. Grassi’s introduction, Dr. Gladden invited him over to the stage with an inside joke. While I may never know what the inside joke was, I was happy to see that scientists of such high caliber still make the time to have a good sense of humor.

“What are the limitations? This has been a question in our field for decades,” Dr. Grassi stated for his opening remark. He then briefly talked about tools previously used for functional evaluation of oxidative metabolism during incremental and constant work rate exercise and suggested some relatively new approaches [i.e., fractional O2 extraction by near-infrared spectroscopy (NIRS) and mitochondrial respiration by high resolution respirometry]. I won’t go into much detail, but it is important to note that the majority of his data showed hypoxia resulting upstream of mitochondrial respiration. The other takeaway was that there is no change in O2 extraction during the initial 10 seconds of exercise onset. However, this O2 extraction is decreased in pathological conditions and metabolic diseases. But, wait, there’s good news! Training does help, and the use of new tools can allow us to place our finger on the complex limitation(s) problem.

Dr. Carsten Lundby (University of Copenhagen), the second speaker, discussed some of his recent work on VO2max which shows that there is a functional reserve for O2 diffusion that is not utilized during exercise in normoxia, or when removing the red blood cells that have been gained with exercise training. Furthermore, his data shows that this is also seen when VO2max returns to pre-training levels. More information is available. 

Dr. Lundby highly recommended reading the Dallas Bed Rest Study to those who are new to this field or for those who have yet to read it. There is a 40-year follow-up of the study.

frog or horseDavid C. Poole, Ph.D., FACSM (Kansas State University) followed Dr. Lundby and focused his talk on matching intramuscular O2 delivery/O2 uptake and peripheral O2 diffusion. He began by suggesting that science is dependent on our perspective and provides an image of a frog, or is it a horse? Take a look at the image and decide for yourself. He then suggested that we must take a black box approach to understanding muscle energetics and explained that it may not be what O2 expenditure reveals, but rather what it conceals. Here are the main three conclusions from Dr. Poole’s talk:

1) Fast twitch fibers regulate QO2/VO2 such that PO2 is lower vs. slow twitch fibers with profound metabolic implications;

2) Exercise training & nitrate supplementation can both increase QO2/VO2 ratio and support faster VO2 kinetics, thereby increasing exercise capacity in health and disease; and

3) Priori studies relating heterogeneity/PO2 changes to O2 transport efficacy across physiologic and pathologic perturbations are required.

The last talk began with Russell T. Hepple, Ph.D., (University of Florida) disclosing that he is a mitochondriac. Dr. Hepple states that he believes the following statement is inaccurate:  mitochondrial O2 availability during exhaustive contractions directly constrains mitochondrial respiration. He then provides data to support his argument, including unpublished data showing that muscle is sensing metabolic disturbances rather than O2. Moreover, he shows an image published in 2013 depicting the mitochondrial interconnections which just happens to be the same interconnections suggested by the great George Brooks in an image published in 1986[i]. Dr. Hepple then suggested that we all read a recent 2017 study which shows the super-complex, higher order organization of the mitochondrial electron transport chain, and does a phenomenal job tying this into Dr. Brian Glancy’s work on the mitochondrial grid structure which was presented in one of the initial symposiums of this IPE conference.

In closing, I’m very happy that I decided to stay for this last symposium as I gained a lot of knowledge and a new interest for mitochondria. Who knows, maybe I’ll even become a mitochondriac one day!

Read part 1 of this series: "Can Exercise Fill the Reductionist Gap? Reflections on Dr. Michael Joyner's Keynote."
Read part 2 of this series: "Are Exercise 'Mimetics' a Realistic Substitute for Exercise Training? Reflections on the Debate." 
Read part 3 of this series: "Exercise and Energy Restriction to Improve Health: Recent Research." 
Read part 4 of this series: "Molecular Transducers of Physical Activity (MoTrPac) Update." 
Read part 5 of this series: "Metabolic Flexibility in Health & Disease: A Symposium Summary." 
Read part 6 of this series: "How Exercise Promotes Brain Health in Aging." 
Read part 7 of this series: "Molecular Transducers of Exercise-Induced Muscle Hypertrophy: A Symposium Summary." 
Read part 8 of this series: "Exercise Pressor Reflex Function in Health and Disease." 
Read part 9 of this series: "Do Genetics Influence Exercise Capacity and Trainability?" 

Jorge Granados, M.S., is a Ph.D. Student studying Exercise Physiology at Texas A&M University. He is also a Graduate Research Assistant in the Biology of Physical Activity Laboratory. 

[i] Kirkwood et al. Am J Physiol Cell. 251(20): C395-402, 1986