Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival

Cell Death Dis. 2015 Jul 30;6(7):e1835. doi: 10.1038/cddis.2015.202.

Abstract

The survival of a cell depends on its ability to meet its energy requirements. We hypothesized that the mitochondrial reserve respiratory capacity (RRC) of a cell is a critical component of its bioenergetics that can be utilized during an increase in energy demand, thereby, enhancing viability. Our goal was to identify the elements that regulate and contribute to the development of RRC and its involvement in cell survival. The results show that activation of metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism. Notably, we identified mitochondrial complex II (cII) as a target of these metabolic sensors and the main source of RRC. Moreover, we show that RRC, via cII, correlates with enhanced cell survival after hypoxia. Thus, for the first time, we show that metabolic sensors via Sirt3 maximize the cellular RRC through activating cII, which enhances cell survival after hypoxia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Hypoxia / genetics
  • Cell Respiration / genetics
  • Cell Survival
  • Electron Transport Complex II / genetics
  • Electron Transport Complex II / metabolism*
  • Gene Expression Regulation
  • Humans
  • Mitochondria / metabolism*
  • Muscle Cells / cytology
  • Muscle Cells / metabolism*
  • Oxidative Phosphorylation
  • Phosphotransferases (Phosphate Group Acceptor) / genetics
  • Phosphotransferases (Phosphate Group Acceptor) / metabolism
  • Primary Cell Culture
  • Pyruvate Dehydrogenase Complex / genetics
  • Pyruvate Dehydrogenase Complex / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Sirtuin 3 / antagonists & inhibitors
  • Sirtuin 3 / genetics
  • Sirtuin 3 / metabolism*

Substances

  • Pyruvate Dehydrogenase Complex
  • RNA, Small Interfering
  • Electron Transport Complex II
  • AMP-dependent kinase (ATP-forming)
  • Phosphotransferases (Phosphate Group Acceptor)
  • SIRT3 protein, human
  • Sirtuin 3