Regulation of mitochondrial temperature in health and disease

El-Gammal, Zaynab; Nasr, Mohamed; Elmehrath, Ahmed O.; Salah, Radwa Ayman; Saad, Shams M.; El‐Badri, Nagwa

doi:10.1007/s00424-022-02719-2

Cited by 25 publications

(11 citation statements)

References 84 publications

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“…To evaluate this activity, isolated mitochondria were subjected to different conditions and labeled with calcein-AM, and their fluorescence intensity was measured using nFCM to gauge esterase activity (Figure A). Recent studies indicate that human mitochondria can reach temperatures as high as 50 °C during intense metabolic processes such as oxidative phosphorylation, , suggesting that mitochondria might sustain efficient functionality at elevated temperatures. In contrast, photothermal therapy typically involves temperatures ranging from subcoagulative (43–55 °C) to coagulative (55–100 °C), aiming to induce rapid cell death through protein denaturation and cell membrane damage .…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry

Su,

Gao,

Tian

et al. 2024

Anal. Chem.

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Monitoring mitochondrial esterase activity is crucial not only for investigating mitochondrial metabolism but also for assessing the effectiveness of mitochondrial-targeting prodrugs. However, accurately detecting esterase activity within mitochondria poses challenges due to its ubiquitous presence in cells and the uncontrolled localization of fluorogenic probes. To overcome this hurdle and reveal variations among different mitochondria, we isolated mitochondria and preserved their activity and functionality in a buffered environment. Subsequently, we utilized a laboratory-built nano-flow cytometer in conjunction with an esterase-responsive calcein-AM fluorescent probe to measure the esterase activity of individual mitochondria. This approach enabled us to investigate the influence of temperature, pH, metal ions, and various compounds on the mitochondrial esterase activity without any interference from other cellular constituents. Interestingly, we observed a decline in the mitochondrial esterase activity following the administration of mitochondrial respiratory chain inhibitors. Furthermore, we found that mitochondrial esterase activity was notably higher in the presence of a high concentration of ATP compared to that of ADP and AMP. Additionally, we noticed a correlation between elevated levels of complex IV and increased mitochondrial esterase activity. These findings suggest a functional connection between the mitochondrial respiratory chain and mitochondrial esterase activity. Moreover, we detected an upsurge in mitochondrial esterase activity during the early stages of apoptosis, while cellular esterase activity decreased. This highlights the significance of analyzing enzyme activity within specific organelle subregions. In summary, the integration of a nano-flow cytometer and fluorescent dyes introduces a novel method for quantifying mitochondrial enzyme activity with the potential to uncover the alterations and unique functions of other mitochondrial enzymes.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry

Su,

Gao,

Tian

et al. 2024

Anal. Chem.

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“…Mitochondrial temperature is a by-product of the OXPHOS which is intimately linked with the mitochondrial dysfunctions [53]. It has been reported that “Mitochondria are physiologically maintained at close to 50°C”, suggesting their warmer temperature than the surrounding [54].…”

Section: Discussionmentioning

confidence: 99%

TRPV4 modulation affects mitochondrial parameters in adipocytes and its inhibition upregulates lipid accumulation

Kumar,

Acharya,

Kumar

et al. 2024

Preprint

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Enhanced lipid-droplet formation by adipocytes is a complex process and relevant for obesity. Using knock-out animals, involvement of TRPV4, a thermosensitive ion channel in the obesity has been proposed. However, exact role/s of TRPV4 in adipogenesis and obesity remain unclear and contradictory. Here we used in vitro culture of 3T3L-1 preadipocytes and primary murine-mesenchymal stem cells as model systems, and a series of live-cell-imaging to analyse the direct involvement of TRPV4 exclusively at the adipocytes that are free from other complex signalling as expected in in-vivo condition. Functional TRPV4 is endogenously expressed in pre- and in mature-adipocytes. Pharmacological inhibition of TRPV4 enhances differentiation of preadipocytes to mature adipocytes, increases expression of adipogenic and lipogenic genes, enhances cholesterol, promotes bigger lipid-droplet formation and reduces the lipid droplet temperature. TRPV4 regulates mitochondrial-temperature, Ca2+-load, ATP, superoxides, cardiolipin, membrane potential (ΔΨm), and lipid-mitochondrial contact sites. TRPV4 also regulates the extent of actin fibres, affecting the cells mechanosensing ability. These findings link TRPV4-mediated mitochondrial changes in the context of lipid-droplet formation involved in adipogenesis and confirms the direct involvement of TRPV4 in adipogenesis. These findings may have broad implication in treating adipogenesis and obesity in future.

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“…Similarly, considering that heat generation is an inescapable cellular function of metabolically active mitochondria, a loss of this activity, as in cases of mitochondrial disease, may compromise the maintenance of intracellular temperature or induce futile cycles of cytosolic ATP generation and usage that may have profound metabolic effects. This could be a crucial aspect of mitochondrial pathology 66 and may also influence progression in other metabolic diseases, including cancer 67 . Some of these and related issues are discussed in the recent paper of Fahimi and colleagues 68 .…”

Section: Biological Implications Of High Mitochondrial Temperaturementioning

confidence: 99%

Mitochondrial temperature homeostasis resists external metabolic stresses

Terzioglu,

Veeroja,

Montonen

et al. 2023

Preprint

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Based on studies with a fluorescent reporter dye, Mito Thermo Yellow, and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to mitochondria, the temperature of active mitochondria in four mammalian and one insect cell-line was estimated to be up to 15 °C above that of the external environment to which the cells were exposed. High mitochondrial temperature was maintained in the face of a variety of metabolic stresses, including substrate starvation or modification, decreased ATP demand due to inhibition of cytosolic protein synthesis, inhibition of the mitochondrial adenine nucleotide transporter and, if an auxiliary pathway for electron transfer was available via the alternative oxidase, even respiratory poisons acting downstream of complex I. We propose that the high temperature of active mitochondria is an inescapable consequence of the biochemistry of oxidative phosphorylation and is homeostatically maintained as a primary feature of mitochondrial metabolism.IMPACT STATEMENTMitochondria are at least 15 °C hotter than their external environment in living cells. In response to diverse metabolic stresses, mitochondrial temperature re-adjusts to this value whenever possible.

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Regulation of mitochondrial temperature in health and disease

Cited by 25 publications

References 84 publications

Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry

Mitochondrial Esterase Activity Measured at the Single Organelle Level by Nano-flow Cytometry

TRPV4 modulation affects mitochondrial parameters in adipocytes and its inhibition upregulates lipid accumulation

Mitochondrial temperature homeostasis resists external metabolic stresses

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