A mitochondrial bioenergetic etiology of disease

J Clin Invest. 2013 Apr;123(4):1405-12. doi: 10.1172/JCI61398. Epub 2013 Apr 1.


The classical Mendelian genetic perspective has failed to adequately explain the biology and genetics of common metabolic and degenerative diseases. This is because these diseases are primarily systemic bioenergetic diseases, and the most important energy genes are located in the cytoplasmic mitochondrial DNA (mtDNA). Therefore, to understand these "complex" diseases, we must investigate their bioenergetic pathophysiology and consider the genetics of the thousands of copies of maternally inherited mtDNA, the more than 1,000 nuclear DNA (nDNA) bioenergetic genes, and the epigenomic and signal transduction systems that coordinate these dispersed elements of the mitochondrial genome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics
  • Energy Metabolism / genetics
  • Epigenesis, Genetic
  • Genetic Predisposition to Disease
  • Genome, Mitochondrial
  • Human Migration
  • Humans
  • Metabolic Diseases / genetics*
  • Metabolic Diseases / metabolism*
  • Mutation
  • Neuromuscular Diseases / genetics
  • Neuromuscular Diseases / metabolism


  • DNA, Mitochondrial