Mitochondrial Ca2+ homeostasis: mechanism, role, and tissue specificities

Abstract

Mitochondria from every tissue are quite similar in their capability to accumulate Ca²⁺ in a process that depends on the electrical potential across the inner membrane; it is catalyzed by a gated channel (named mitochondrial Ca²⁺ uniporter), the molecular identity of which has only recently been unraveled. The release of accumulated Ca²⁺ in mitochondria from different tissues is, on the contrary, quite variable, both in terms of speed and mechanism: a Na⁺-dependent efflux in excitable cells (catalyzed by NCLX) and a H⁺/Ca²⁺ exchanger in other cells. The efficacy of mitochondrial Ca²⁺ uptake in living cells is strictly dependent on the topological arrangement of the organelles with respect to the source of Ca²⁺ flowing into the cytoplasm, i.e., plasma membrane or intracellular channels. In turn, the structural and functional relationships between mitochondria and other cellular membranes are dictated by the specific architecture of different cells. Mitochondria not only modulate the amplitude and the kinetics of local and bulk cytoplasmic Ca²⁺ changes but also depend on the Ca²⁺ signal for their own functionality, in particular for their capacity to produce ATP. In this review, we summarize the processes involved in mitochondrial Ca²⁺ handling and its integration in cell physiology, highlighting the main common characteristics as well as key differences, in different tissues.

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

“…Appropriate calcium levels can enhance mitochondrial function; however, excessive levels of calcium disturb the electrochemical gradient in mitochondria (Pizzo et al, 2012) and can induce mitochondrial apoptosis (Keinan et al, 2013). To further understand mitochondrial metabolism during inflammation, we measured the calcium content both in muscle and isolated mitochondria, and found mitochondrial calcium content was significantly increased.…”

Effects of high ambient temperature on fish sperm plasma membrane integrity and mitochondrial activity — A flow cytometric study

“…Our aim in this study was to assess the usefulness of flow cytometry to detect the changes of plasma membrane integrity and mitochondrial transmembrane potential of fish spermatozoa, incubated at different temperatures (20,25, 30 and 40 °C) for 10 and 30 minutes, respectively, to reveal if this increase of ambient temperature can lead to cell death or mitochondrial membrane depolarization.…”

Mitofusin 2 ablation increases endoplasmic reticulum–mitochondria coupling

“…As to the former, Vance (3) firstly described a partially purified microsomal subfraction pulled down with mitochondria (fraction X, later renamed "mitochondria-associated membrane," MAM) that was found to be enriched in phosphatidylserine synthase and several enzymes involved in lipid and glucose metabolism, cholesterol, and ceramide biosynthesis (4,5). As far as Ca 2+ signaling is concerned, the ERmitochondria axis plays a critical role in cell Ca 2+ homeostasis (6)(7)(8). In parallel, increases of Ca 2+ within mitochondria are essential in tuning physiological organelle activity (9,10) and in modulating the process of cell death (6,8,11).…”