Mitochondrial calcium transport and the redox nature of the calcium-induced membrane permeability transition

Abstract

Mitochondria possess a Ca transport system composed of separate Ca influx and efflux pathways. Intramitochondrial Ca concentrations regulate oxidative phosphorylation, required for cell function and survival, and mitochondrial redox balance, that participates in a myriad of signaling and damaging pathways. The interaction between Ca accumulation and redox imbalance regulates opening and closing of a highly regulated inner membrane pore, the membrane permeability transition pore (PTP). In this review, we discuss the regulation of the PTP by mitochondrial oxidants, reactive nitrogen species, and the interactions between these species and other PTP inducers. In addition, we discuss the involvement of mitochondrial redox imbalance and PTP in metabolic conditions such as atherogenesis, diabetes, obesity and in mtDNA stability.

Mitochondrial Morphology Regulates Organellar Ca2+Uptake and Changes Cellular Ca2+Homeostasis

“…2), possibly due to its effects of decreasing  (Fig. 4), a known inducer of this process (see Vercesi et al, 2018 for a review). MFN2 KD also significantly changes mitochondrial Ca 2+ homeostasis: it decreases both Ca 2+ uptake rates and Ca 2+ retention capacity in mitochondria (Fig.…”

“…Intracellular and intramitochondrial Ca 2+ , on the other hand, are central metabolic regulators, affecting the activity of both cytosolic and mitochondrial metabolic pathways (Clapham, 2004;Gunter and Sheu, 2009;Vercesi et al, 2018). While the close interaction between the ER and mitochondria is important for adequate signaling, recent studies have shown that ER-mitochondrial interactions increase excessively in high fat diets, resulting in mitochondrial Ca 2+ overload and dysfunction.…”

“…Mitochondrial Ca 2+ uptake presents very high capacity, allowing for the accumulation of large quantities of the ion, although it is low in affinity relative to the ER. Within mitochondria, Ca 2+ ions act as regulators of important metabolic pathways, determining ATP synthesis rates (Clapham, 2004;Gunter and Sheu, 2009;Vercesi et al, 2018). Excessive mitochondrial Ca 2+ uptake, however, is disruptive for cell integrity under a number of pathological conditions, including stroke, ischemic heart disease and inflammatory liver conditions (Duchen, 2000;Brookes et al, 2004;Murphy and Steenbergen, 2008;Nicholls, 2009;Arruda and Hotamisligil, 2015).…”

“…Excessive mitochondrial Ca 2+ uptake, however, is disruptive for cell integrity under a number of pathological conditions, including stroke, ischemic heart disease and inflammatory liver conditions (Duchen, 2000;Brookes et al, 2004;Murphy and Steenbergen, 2008;Nicholls, 2009;Arruda and Hotamisligil, 2015). Under these conditions, dysfunction is associated with the mitochondrial permeability transition, a loss of inner mitochondrial membrane impermeability promoted by Ca 2+ overload, oxidative imbalance and protein missfolding (Figueira et al, 2013;Biasutto et al, 2016;Vercesi et al, 2018).…”

Functional Changes Induced by Short Term Caloric Restriction in Cardiac and Skeletal Muscle Mitochondria

“…A mitochondrial phenomenon associated with many age-related pathological conditions is the mitochondrial permeability transition (mPT), a sudden increase in inner mitochondrial membrane permeability (Hunter & Haworth, 1979a;Haworth & Hunter, 1979b, Haworth & Hunter, 1979, reviewed by Chinopoulus, 2018Vercesi et al, 2018). mPT results in loss of ion gradients and metabolite accumulation, hampering oxidative phosphorylation.…”