Mitochondria are physiologically maintained at close to 50 °C

PLoS Biol. 2018 Jan 25;16(1):e2003992. doi: 10.1371/journal.pbio.2003992. eCollection 2018 Jan.

Abstract

In endothermic species, heat released as a product of metabolism ensures stable internal temperature throughout the organism, despite varying environmental conditions. Mitochondria are major actors in this thermogenic process. Part of the energy released by the oxidation of respiratory substrates drives ATP synthesis and metabolite transport, but a substantial proportion is released as heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria, we measured mitochondrial temperature in situ under different physiological conditions. At a constant external temperature of 38 °C, mitochondria were more than 10 °C warmer when the respiratory chain (RC) was fully functional, both in human embryonic kidney (HEK) 293 cells and primary skin fibroblasts. This differential was abolished in cells depleted of mitochondrial DNA or treated with respiratory inhibitors but preserved or enhanced by expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling protein 1. The activity of various RC enzymes was maximal at or slightly above 50 °C. In view of their potential consequences, these observations need to be further validated and explored by independent methods. Our study prompts a critical re-examination of the literature on mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fibroblasts / physiology
  • Fluorescent Dyes
  • HEK293 Cells
  • Hot Temperature
  • Humans
  • Mitochondria / physiology*
  • Mitochondrial Membranes / physiology
  • Mitochondrial Proteins / metabolism
  • Oxidoreductases / metabolism
  • Plant Proteins / metabolism
  • Primary Cell Culture
  • Skin
  • Temperature
  • Thermogenesis / physiology*
  • Uncoupling Protein 1 / metabolism

Substances

  • Fluorescent Dyes
  • Mitochondrial Proteins
  • Plant Proteins
  • UCP1 protein, human
  • Uncoupling Protein 1
  • Oxidoreductases
  • alternative oxidase

Grants and funding

European Research Council (grant number 232738). Received by HTJ. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Academy Professorship (grant number 256615). Received by HTJ. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Academy of Finland (grant number FinMIT CoE 272376). Received by HTJ. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ouvrir Les Yeux (OLY). Received by PB and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Association Française contre l’Ataxie de Friedreich (AFAF). Received by PB and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Association contre les Maladies Mitochondriales (AMMi). Received by DC, PB, MR, and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Association d’Aide aux Jeunes Infirmes (AAJI). Received by PB and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. E-Rare (grant number E-rare Genomit). Received by DC, PB, MR, and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ANR (grant number ANR MITOXDRUGS-DS0403). Received by DC, PB, MR, and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ANR (grant number ANR FIFA2-12-BSV1-0010). Received by DC, PB, MR, and PR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.