Thermogenesis was activated by respiratory substrate of complex

In this report, thermogenesis was activated by respiratory substrate of complex 1 in media without added ATP. At present, it is not clear to us what the role of SERCA 1 in BAT mitochondria is. The following hypothetical possibilities are raised: in the particular case of BAT, Ca2+ would be released in mitochondria via the MAM as previously reported for other tissues. However the excess of Ca2+ would not be alleviated solely via MAM; it could also be pumped out of the mitochondria by the SERCA 1 located in mitochondrial BOC-D-FMK cristae; SERCA 1 would be involved in the activation of thermogenesis promoted by the addition of low Ca2+ concentrations in the assay medium. In favor of this hypothesis are the following findings: the Ca2+ concentration needed for halfmaximal heat production is in the same range as the Ca2+ concentration needed to pump Ca2+ in vesicles derived from skeletal muscle sarcoplasmic reticulum ; Ca2+ activates only heat production and has no influence in the rate of oligomycin-sensitive ATP synthesis; In the presence of Ca2+, there is a significant discrepancy between the rates of oxygen BTTAA consumption and heat production. This could be best seen in uncoupled mitochondria where all energy derived from respiration is dissipated as heat and none is used for oligomycin-sensitive ATP synthesis. Although Ca2+ activated both respiration and heat production, the enhancement of respiration was,30%, while activation of heat production was,60%. The amount of energy derived from each K O2 consumed is 52.6 kcal. In absence of Ca2+, the heat measured was slightly higher than the heat calculated from K O2 consumed, while in presence of Ca2+ it was 60% higher. This discrepancy may indicate that Ca2+ activates a thermogenic process that is not active in the presence of excess EGTA. The fact that heat production in the presence of either Ca2+ or EGTA was impaired by rotenone and cyanide indicates that the activation of heat production by Ca2+ is linked to flux of electrons through the cytochrome chain. SERCA 1 has been shown to be able to interconvert different forms of energy to synthesize ATP from ADP and Pi. These include energies derived from a gradient of Ca2+, pH, water activity or even thermal energy.

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