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Mitochondrial energetics and therapeutics.

Douglas C Wallace¹, Weiwei Fan, Vincent Procaccio

¹Center for Molecular and Mitochondrial Medicine and Genetics and Departments of Biological Chemistry, Ecology and Evolutionary Biology, and Pediatrics, University of California at Irvine, Irvine, California 92697-3940, USA. dwallace@uci.edu

Annual Review of Pathology

|January 19, 2010

Summary

Mitochondrial dysfunction underlies many diseases, but metabolic therapies fail due to poor understanding of bioenergetics. A systems approach, like the ketogenic diet, offers potential for new bioenergetic therapeutics.

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Area of Science:

Cell Biology
Metabolic Diseases
Aging

Background:

Mitochondrial dysfunction is implicated in degenerative diseases, cancer, and aging.
Cellular bioenergetics is central to these conditions.
Current metabolic therapies are ineffective due to limited understanding of bioenergetics.

Purpose of the Study:

To explore the role of bioenergetics as an interface between the environment and the cell.
To re-evaluate the ketogenic diet as a systems approach to metabolic therapy.
To understand how metabolic shifts impact cellular processes.

Main Methods:

Analysis of metabolic shifts from carbohydrate to fatty acid/ketone metabolism.
Investigating modulation of metabolism, signal transduction, and the epigenome.
Reviewing historical success of the ketogenic diet.

Main Results:

The ketogenic diet represents a successful historical systems approach to metabolism.
Shifting metabolism impacts key cellular pathways.
Bioenergetics is a critical link between environment and cellular function.

Conclusions:

A systems approach is needed for effective metabolic therapies.
The ketogenic diet demonstrates the potential of bioenergetic therapeutics.
Further research into metabolic modulation can advance treatment strategies.