The multiple facets of mitochondrial regulations controlling cellular thermogenesis

Abstract

Understanding temperature production and regulation in endotherm organisms becomes a crucial challenge facing the increased frequency and intensity of heat strokes related to global warming.Mitochondria, located at the crossroad of metabolism, respiration, Ca 2+ homeostasis and apoptosis, were recently proposed to further act as cellular radiators, with an estimated inner temperature reaching 50°C in common cell lines. This inner thermogenesis might be further exacerbated in organs devoted to produce consistent efforts as muscles, or heat as brown adipose tissue, in response to acute solicitations. Consequently, pathways promoting respiratory chain uncoupling and mitochondrial activity, such as Ca 2+ uxes, uncoupling proteins, futile cycling and substrate supplies, provide the main processes controlling heat production and cell temperature. The mitochondrial thermogenesis might be further ampli ed by cytoplasmic mechanisms promoting the over-consumption of ATP pools.Considering these new thermic paradigms, we discuss here all conventional wisdoms linking mitochondrial functions to cellular thermogenesis in different physiological conditions. HighlightsBeyond its role as the principal source of ATP production, mitochondria can be considered as cellular radiators, with a possible local temperature of 50°C. This physiological contribution to heat production is regulated by many mechanisms targeting mitochondrial activity levels, and can be further stimulated by uncoupling the respiratory chain and membrane potential from ATP synthesis, to respond to drastic cold stresses. In addition, exergonic reactions using large ATP amounts in cell functions, like muscle shivering or Ca 2+ leak from the SR, can contribute to generate heat by inducing an over-stimulation of mitochondrial activity to replenish ATP pools. Cell variations in thermal ows might thus promote heterogeneous subcellular temperature gradients that might contribute to novel regulatory pathways controlling cell physiology. Internal Heat Production In EndothermsBody temperature in endotherms, such as mammals, is crucial for the management of most biological functions. The ability to produce internal heat and maintain a constant body temperature was acquired during animal evolution, and is closely linked to original processes controlling energy metabolism. Indeed, an increased metabolic rate in endotherm species produces su cient heat to raise body temperature, even at rest (Legendre et Davesne 2020).Thermodynamics laws help to understand the link between heat production and energy metabolism.Energetic metabolism combines catabolic reactions, which break down molecules into smaller units, and anabolic reactions, which promote the synthesis of complex molecules from smaller units. Catabolic reactions are spontaneous and exergonic, i.e. more energy is released than consumed, whereas anabolic reactions are non-spontaneous endergonic reactions, requiring energy input from exergonic reactions.

Comparative Proteomic Analysis Provides New Insights into the Molecular Basis of Thermal-Induced Parthenogenesis in Silkworm (Bombyx mori)

“…The increase of pyrimidine metabolism and increasing abundance of RAD50 may be a response to DNA damage [ 55 , 56 ]. The decrease in the thermogenesis pathway and oxidative phosphorylation mediates the regulation of energy metabolism, as well as the balance between heat production and dissipation during thermal treatment, which promotes adaptation to high-temperature environments [ 57 ]. It seems that PL has a more effective response to buffer thermal stress than AL.…”

Cell Phone Radiation Exposure Limits and Engineering Solutions

“…Inside cells, small elements such as organelles and enzymes vary in terms of their shape, function, and vulnerability to RFR. The anatomical, electrical, and thermal structures of mitochondria, in particular [ 114 , 115 ], run entirely counter to IEEE-ICNIRP’s philosophy of oversimplification.…”

“…In addition, the results of Figure 6 are far from extending even to cellular sizes ( Table 2 , Cell sizes in humans compared to IEEE-ICNIRP averaging). Therefore, it is probable that even higher psSAR values would be obtained by reducing cube sizes below 0.01 g. In addition, these estimations, obtained using a four-slab (skin, fat, bone, brain) flat phantom, fall far short of representing the true complexity and anisotropy of cells and mitochondria, both in terms of micro-anatomy and temperature uniformity [ 114 , 115 ].…”

Targeted metabolomics detects a putatively diagnostic signature in plasma and dried blood spots from head and neck paraganglioma patients

“…Accumulation of dAdo may also block transmethylation reactions through the inactivation of S-adenosylhomocysteine hydrolase (SAHH), thus promoting the buildup of the methyltransferase inhibitor S-adenosyl-L-homocysteine (SAH), possibly implicated in the hypermethylated HNPGL phenotype [ 19 ]. Furthermore, high 2′-deoxy-ATP/ATP ratios and dAdo availability could facilitate the synthesis of adenosine 2′-diphosphoribose, an endogenous superagonist of the transient receptor potential (TRP) melastatin 2 (TRPM2) plasma membrane cation channel that, under ROS-induced stress, controls Ca2+ fluxes and hence Ca2+ signaling, mitochondrial respiratory uncoupling and immune function [ 51 – 53 ]. Sustained Ca2+ influx and oxidative stress rapidly reach a cytotoxic and apoptotic threshold in normal cells.…”