Mitochondria: great balls of fire

Abstract

Recent experimental studies indicate that mitochondria in mammalian cells are maintained at temperatures of at least 50 °C. While acknowledging the limitations of current experimental methods and their interpretation, we here consider the ramifications of this finding for cellular functions and for evolution. We consider whether mitochondria as heat-producing organelles had a role in the origin of eukaryotes and in the emergence of homeotherms. The homeostatic responses of mitochondrial temperature to externally applied heat imply the existence of a molecular heat-sensing system in mitochondria. While current findings indicate high temperatures for the innermost compartments of mitochondria, those of the mitochondrial surface and of the immediately surrounding cytosol remain to be determined. We ask whether some aspects of mitochondrial dynamics and motility could reflect changes in the supply and demand for mitochondrial heat, and whether mitochondrial heat production could be a factor in diseases and immunity.

Keywords: cold‐shock; eukaryote origins; heat‐shock; homeothermy; immunity; mitochondria; mitochondrial disease; mitochondrial dynamics; temperature gradients; thermogenesis.

Fig. 1

Stresses influencing mitochondrial temperature and heat production. (A, B) MTY (Mito Thermo Yellow) fluorescence traces (arbitrary values) indicating mitochondrial temperature changes resulting from (A) cold shock (37 → 31 °C) and (B) heat shock (37 → 40 °C), applied at time t = 0 (first vertical arrow) to cultured mouse embryo fibroblasts. Oligomycin was added to 5 μm at the indicated times (second vertical arrow). Same materials, methods, and calibration steps as described by Terzioglu et al. [2]. Shown are representative MTY fluorescence traces, annotated to indicate mean temperature shifts based on (A) 5 and (B) 3 independent experiments. Note that increased fluorescence indicates cooling and vice versa. Calibration values for the illustrated experiments are shown as black bars against yellow background. For source data, see Table S1. (C) Summary of stresses known [2] (in black) or hypothesized (in red) to induce homeostatic responses of mitochondrial temperature. Double‐headed arrows indicate processes assumed to operate in both directions. Black line: OMM (outer mitochondrial membrane), red line and blue line: respectively, inner boundary membrane and cristal membrane, considered together as IMM (inner mitochondrial membrane), cream oval: IMS (mitochondrial inter‐membrane space), pale blue oval: mitochondrial matrix.

Fig. 2

Meltome analysis of human proteins. Mean T _m (melting temperature, °C to nearest degree, shown in yellow circles) of proteins assigned to different subcellular compartments, based on the analysis presented in Fig. S1. Gray line: ER (endoplasmic reticulum) membrane, gray oval: ER lumen, turquoise circle: nucleoplasm, bold gray dotted line: nuclear envelope, white background: cytosol. Other symbols as in Fig. 1C.