Revisiting Mitochondrial Bioenergetics: Experimental Considerations for Biological Interpretation
Bibliographic record
Abstract
Mitochondria are essential for energy homeostasis and redox balance in many tissues of the body. This dissertation includes a series of studies investigating mitochondrial bioenergetics during muscle use (exercise), disuse (immobilization), and disease (obesity, cardiomyopathy) and the impact of nutrition under these conditions. In chapter 2, we provide a perspective highlighting the importance of measuring submaximal mitochondrial kinetics. In chapter 3, we study the role of mitochondrial “dysfunction”, adipose tissue inflammation, and gut dysbiosis within obesity in mice, induced by either excess fat intake or excess caloric consumption. We establish that high-fat diets may cause many of the metabolic changes during obesity. In chapter 4, we examine the ability of the dietary nitrate to prevent high-fat diet-induced impairments in cardiometabolic health and mitochondrial bioenergetics in mice. Nitrate supplementation prevented the increase in mitochondrial reactive oxygen species within the left ventricle, which occurred along with protective effects of nitrate on cardiac function and was partially due to beneficial changes in the gut microbiome. In chapter 5, we examine the influence of nitrate supplementation on skeletal muscle calcium handling, mitochondrial bioenergetics, and muscle force production in healthy mice. While nitrate supplementation did not alter mitochondrial respiration in healthy mice, nitrate increased the transfer of ADP from cellular organelles to mitochondria. In chapter 6, we examine the effects of nitrate supplementation on skeletal muscle metabolism during limb immobilization in mice. We report that nitrate prevented mitochondrial dysregulation following single-limb immobilization. In chapter 7, we examine if ketone bodies are an effective substrate to support mitochondrial respiration at rest and during exercise. However, in all conditions, the ability of ketone bodies to drive mitochondrial respiration was minimal. In chapter 8, we examine mitochondrial substrate sensitivity during exercise and post-exercise recovery in endurance-trained males. We show that the decline in mitochondrial ADP sensitivity during intense exercise was correlated with the extent of glycogen depletion. In summary, this dissertation has identified that mitochondria play an important role in both health and disease. Alterations in mitochondrial bioenergetics are evident in numerous clinical situations and can be influenced by nutritional compounds, with effects on whole-body outcomes.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.022 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.016 |
| Scholarly communication | 0.007 | 0.015 |
| Open science | 0.007 | 0.004 |
| Research integrity | 0.005 | 0.013 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".