4.5 Review Book Chapter

Mitochondrial Energetics and Therapeutics

Journal

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev.pathol.4.110807.092314

Keywords

mitochondria; oxidative phosphorylation; mitochondrial disorders; redox state; mitochondrial therapies

Categories

Funding

  1. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK073691] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS041850, R01NS021328] Funding Source: NIH RePORTER
  3. NATIONAL INSTITUTE ON AGING [P50AG016573, R01AG024373] Funding Source: NIH RePORTER
  4. NIA NIH HHS [P50 AG016573, AG24373, R01 AG024373, AG16573, R01 AG024373-05] Funding Source: Medline
  5. NIDDK NIH HHS [DK73691, R01 DK073691] Funding Source: Medline
  6. NINDS NIH HHS [R01 NS021328-24, R01 NS021328-25, R01 NS041850-06, R01 NS041850, NS41850, R01 NS21328, R01 NS021328] Funding Source: Medline
  7. Autism Speaks [AS5668] Funding Source: Medline

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Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise front 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 in appreciation of the ketogenic diet and the potential for bioenergetic therapeutics.

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