Nucleus-encoded regulators of mitochondrial function: Integration of respiratory chain expression, nutrient sensing and metabolic stress

Richard C. Scarpulla*

*Corresponding author for this work

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Nucleus-encoded regulatory factors are major contributors to mitochondrial biogenesis and function. Several act within the organelle to regulate mitochondrial transcription and translation while others direct the expression of nuclear genes encoding the respiratory chain and other oxidative functions. Loss-of-function studies for many of these factors reveal a wide spectrum of phenotypes. These range from embryonic lethality and severe respiratory chain deficiency to relatively mild mitochondrial defects seen only under conditions of physiological stress. The PGC-1 family of regulated coactivators (PGC-1α, PGC-1β and PRC) plays an important integrative role through their interactions with transcription factors (NRF-1, NRF-2, ERRα, CREB, YY1 and others) that control respiratory gene expression. In addition, recent evidence suggests that PGC-1 coactivators may balance the cellular response to oxidant stress by promoting a pro-oxidant environment or by orchestrating an inflammatory response to severe metabolic stress. These pathways may serve as essential links between the energy generating functions of mitochondria and the cellular REDOX environment associated with longevity, senescence and disease. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.

Original languageEnglish (US)
Pages (from-to)1088-1097
Number of pages10
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1819
Issue number9-10
DOIs
StatePublished - Sep 1 2012

Keywords

  • Coactivator
  • Metabolic stress
  • Metabolism
  • Mitochondria
  • Nucleomitochondrial interaction
  • Transcription factor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

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