Mitochondrial energy generation disorders: genes, mechanisms, and clues to pathology

J Biol Chem. 2019 Apr 5;294(14):5386-5395. doi: 10.1074/jbc.R117.809194. Epub 2017 Dec 12.

Abstract

Inherited disorders of oxidative phosphorylation cause the clinically and genetically heterogeneous diseases known as mitochondrial energy generation disorders, or mitochondrial diseases. Over the last three decades, mutations causing these disorders have been identified in almost 290 genes, but many patients still remain without a molecular diagnosis. Moreover, while our knowledge of the genetic causes is continually expanding, our understanding into how these defects lead to cellular dysfunction and organ pathology is still incomplete. Here, we review recent developments in disease gene discovery, functional characterization, and shared pathogenic parameters influencing disease pathology that offer promising avenues toward the development of effective therapies.

Keywords: OXPHOS; genetic disease; genomics; mitochondria; mitochondrial disease; respiratory chain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Energy Metabolism*
  • Genetic Diseases, Inborn* / genetics
  • Genetic Diseases, Inborn* / metabolism
  • Genetic Diseases, Inborn* / pathology
  • Humans
  • Mitochondrial Diseases* / genetics
  • Mitochondrial Diseases* / metabolism
  • Mitochondrial Diseases* / pathology
  • Mutation*