Mitochondria are physiologically maintained at close to 50 °C

Chrétien, Dominique; Bénit, Paule; Ha, Hyung‐Ho; Keipert, Susanne; El-Khoury, Riyad; Chang, Young‐Tae; Jastroch, Martin; Jacobs, Howard T.; Rustin, Pierre; Rak, Malgorzata

doi:10.1101/133223

Cited by 28 publications

(36 citation statements)

References 29 publications

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“…This observation is in full agreement with our previous report demonstrating that the Ca 2+ -pattern in mitochondria-enriched neck region of mature spermatozoa is altered in case of TRPV4 activation (Kumar et al 2016). Moreover, the presence of TRPV4 that can act as a thermo-sensitive ion channel (Guler et al, 2002), agrees well with the reports that mitochondria maintain higher temperature than the cytosol (Chrétien et al 2018;Lane N 2018).…”

Section: Presence Of Trp Channels In Mitochondriasupporting

confidence: 93%

“…1996;Duchen et al 1999;Jouaville et al 1995). In addition, for a long time it is well known that the temperature-sensing ability is a unique property of cellular mitochondria, even in isolated conditions though the molecular players involved in this feature are currently unknown (Johnston et al 1994;Kang et al 2008;Chrétien et al 2018). In this work, we demonstrate that the TRPV4 channel localizes to a sub-population of mitochondria in various cell types.…”

Section: Discussionmentioning

confidence: 49%

“…Accordingly mitochondrial Ca 2+ -uptake is a key regulator for cell survival and various functions such as metabolism, secretion and cellular signalling. Within the cell, mitochondria maintain a higher temperature due to their unique ability to sense different temperatures and respond to slight changes in physiological temperatures (Chrétien et al 2018;Lane N 2018). However, candidate proteins present in mitochondria that are involved mediating such mitochondrial functions, including Ca 2+ -transport or temperature sensing, have not been identified yet.…”

Section: Introductionmentioning

confidence: 99%

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TRPV4 interacts with mitochondrial proteins and acts as a mitochondrial structure-function regulator

Kumar

Majhi

Acharya

et al. 2018

Preprint

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TRPV4 has been linked with the development of sensory defects, neuropathic pain, neurodegenerative disorders such as Charcot Marie Tooth disease and various muscular dystrophies. In all these cases mitochondrial abnormalities were tagged as cellular hallmarks and such abnormalities have been reported as key factor for the pathophysiological conditions. Mitochondria also have the unique ability to sense and regulate their own temperature. Here, we demonstrate that TRPV4, a thermosensitive ion channels, localizes to a subpopulation of mitochondria in various cell lines, in primary cells and also in sperm cells. Improper expression and/or function of TRPV4 induce several mitochondrial abnormalities such as low oxidative potential, high Ca 2+ -influx and changes in electron transport chain functions. TRPV4 is also involved in regulation of mitochondrial morphology, smoothness, and fusion -fission events. The C-terminal cytoplasmic region of TRPV4 can localize it to mitochondria and interacts with mitochondrial proteins including Hsp60, Mfn1 and Mfn2. Regulation of mitochondria by TRPV4 may contribute to previously uncharacterized mitochondria-specific functions observed in various cell types. This discovery may help to link TRPV4-mediated channelopathies with mitochondria-mediated diseases.

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Section: Presence Of Trp Channels In Mitochondriasupporting

confidence: 93%

Section: Discussionmentioning

confidence: 49%

Section: Introductionmentioning

confidence: 99%

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TRPV4 interacts with mitochondrial proteins and acts as a mitochondrial structure-function regulator

Kumar

Majhi

Acharya

et al. 2018

Preprint

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“…Fortunately, newer mitochondrial superoxide probes, including MitoB [135,136] and MitoNeoD [137], have been developed to overcome these shortcomings. Another mitochondrial dye, which monitors temperature gradients (mito thermo yellow) has been used to suggest the provocative idea that mitochondria may be physiologically maintained around 50°C [138,139]. …”

Section: 3 Resultsmentioning

confidence: 99%

Methods for imaging mammalian mitochondrial morphology: A prospective on MitoGraph

Harwig

Viana

Egner

et al. 2018

Analytical Biochemistry

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Mitochondria are found in a variety of shapes, from small round punctate structures to a highly interconnected web. This morphological diversity is important for function, but complicates quantification. Consequently, early quantification efforts relied on various qualitative descriptors that understandably reduce the complexity of the network leading to challenges in consistency across the field. Recent application of state-of-the-art computational tools have resulted in more quantitative approaches. This prospective highlights the implementation of MitoGraph, an open-source image analysis platform for measuring mitochondrial morphology initially optimized for use with Saccharomyces cerevisiae. Here Mitograph was assessed on five different mammalian cells types, all of which were accurately segmented by MitoGraph analysis. MitoGraph also successfully differentiated between distinct mitochondrial morphologies that ranged from entirely fragmented to hyper-elongated. General recommendations are also provided for confocal imaging of labeled mitochondria (using mito-YFP, MitoTracker dyes and immunostaining parameters). Widespread adoption of MitoGraph will help achieve a long-sought goal of consistent and reproducible quantification of mitochondrial morphology.

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“…However, the working temperature of human mitochondria has been reported to be as high as 50°C, and the activity of various respiratory chain enzymes was maximum at or slightly above 50°C. (Chrétien et al, 2018), which suggests that the thermal tolerance of mitochondria is much stronger than we expected, at least in humans. Importantly, heat tolerant mitochondria in insects has been suggested by Heinrich et al (2017), as robust mitochondria metabolism can be sustained at temperatures higher than critical thermal maximums (CT max ).…”

Section: Mechanisms Of Heat Susceptibility In Ghost Mothsmentioning

confidence: 52%

Metabolomics reveals the key role of oxygen metabolism in heat susceptibility of an alpine‐dwelling ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae)

et al. 2018

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Ghost moths inhabiting the alpine meadows of the Tibetan Plateau are cold-adapted stenothermal organisms that are susceptible to heat (dead within 7 days at 27 °C exposure). Exploring the metabolic basis of their heat susceptibility would extend our understanding of the thermal biology of alpine-dwelling invertebrates. Here, gas chromatography-mass spectrometry-based metabolomics was combined with physiological and transcriptional approaches to determine the metabolic mechanisms of heat susceptibility in Thitarodes xiaojinensis larvae. The metabolomics results showed that 27 °C heat stress impaired the Krebs cycle and lipolysis in T. xiaojinensis larvae, as demonstrated by the accumulation of intermediary metabolites. In addition, carbohydrate reserves were highly and exclusively consumed, and an anaerobic product, lactate, accumulated. This evidence suggested a strong reliance on glycolysis to anaerobically generate energy. The respiration rate and enzymatic activity test results indicated a deficiency in O metabolism; in addition, the Krebs cycle capacity was not decreased, and the metabolic flux through aerobic pathways was limited. These findings were further supported by the occurrence of hypoxia symptoms in midgut mitochondria (vacuolation and swelling) and increased transcription of hypoxia-induced factor 1-α. Overall, heat stress caused O limitation and depressed the overall intensity of aerobic metabolism in ghost moths, and less efficient anaerobic glycolysis was activated to sustain their energy supply. As carbohydrates were depleted, the energy supply became deficient. Our study presents a comprehensive metabolic explanation for the heat susceptibility of ghost moths and reveals the relationship between O metabolism and heat susceptibility in these larvae.

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Mitochondria are physiologically maintained at close to 50 °C

Cited by 28 publications

References 29 publications

TRPV4 interacts with mitochondrial proteins and acts as a mitochondrial structure-function regulator

TRPV4 interacts with mitochondrial proteins and acts as a mitochondrial structure-function regulator

Methods for imaging mammalian mitochondrial morphology: A prospective on MitoGraph

Metabolomics reveals the key role of oxygen metabolism in heat susceptibility of an alpine‐dwelling ghost moth, Thitarodes xiaojinensis (Lepidoptera: Hepialidae)

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