Goldilocks calcium concentrations and the regulation of oxidative phosphorylation: Too much, too little, or just right

• DOI: 10.1016/j.jbc.2023.102904
• Publication Date: 2023-01-13T07:30:01Z
• Authors: Eloisa A. Vilas-Boas; João Victor Cabra...; Vitor M. Ramos; Camille C. Caldei...; Alicia J. Kowalto...
• Keywords: Goldilocks principle

Calcium (Ca2+) is a key regulator in diverse intracellular signaling pathways and has long been implicated metabolic control mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important Ca2+ buffers affecting cytosolic transients. Excessive matrix known to be deleterious due opening the permeability transition pore (mPTP) consequent membrane potential dissipation, leading swelling, rupture, cell death. Moderate within organelle, on other hand, directly or indirectly activate enzymes, possibly impacting ATP production. Here, we aimed determine quantitative manner if extra- intramitochondrial modulates oxidative phosphorylation mouse liver mitochondria intact hepatocyte lines. To do so, monitored effects more modest versus supraphysiological increases oxygen consumption rates. Isolated present increased respiratory ratios (a measure efficiency) when incubated with low (2.4 ± 0.6 μM) medium (22.0 2.4 concentrations presence complex I-linked substrates pyruvate plus malate α-ketoglutarate, respectively, but not II-linked succinate. In cells, both high led decreased rates, while ideal rates were under physiological conditions. High respiration substrate-dependent manner, mediated by mPTP. Overall, our results uncover Goldilocks effect mitochondria, specific "just right" that phosphorylation.