Mitochondrial Energetics and Therapeutics

By Douglas C. Wallace, W. Fan, Vincent Procaccio. Annual Review of Pathology, 2010

713 citations recorded by the source corpus.

Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics.

Subfields: Clinical Biochemistry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/e579767f58c6e7884a60af3da6b029b6bbe46842

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Citations in the corpus

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging (2013, background): “One of the most conserved and robust phenomena in biology is a progressive decline in mitochondrial function with age, leading to a loss of cellular homeostasis and organismal health (Lanza and Nair, 2010; Wallace et al., 2010).”
Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “74 Integral to this process are key metabolic substrates: pyruvate, fatty acid, and glutamine are metabolized to form acetyl-CoA and alpha-ketoglutarate ( α -kG), respectively.”
Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease. (2013, background): “Assuming common diseases result from partial mitochondrial deficiencies, this could then perturb an array of physiological processes including energy production, REDOX state, Ca2þ homeostasis, ROS production, anabolic and catabolic metabolic pathways, etc. (Wallace et al. 2010).”