Mitochondrial Ca²⁺ channels: Great unknowns with important functions

Abstract 

Mitochondria process local and global Ca²⁺ signals. Thereby the spatiotemporal patterns of mitochondrial Ca²⁺ signals determine whether the metabolism of these organelles is adjusted or cell death is executed. Mitochondrial Ca²⁺ channels of the inner mitochondrial membrane (IMM) actually implement mitochondrial uptake from cytosolic Ca²⁺ rises. Despite great efforts in the past, the identity of mitochondrial Ca²⁺ channels is still elusive. Numerous studies aimed to characterize mitochondrial Ca²⁺ uniport channels and provided a detailed profile of these great unknowns with important functions. This mini-review revisits previous research on the mechanisms of mitochondrial Ca²⁺ uptake and aligns them with most recent findings.

Abbreviations: ANT, adenine nucleotide translocase, ER, endoplasmic reticulum, grp75, glucose-regulated protein 75, IML2, inter membrane loop 2, IMM, inner mitochondrial membrane, IP₃R, inositol 1,4,5-trisphosphate receptor, MAM, mitochondrial-associated ER membrane, MAPK, mitogen-activated kinase, mCa/MiCa, mitochondrial Ca²⁺ channel, MCU, mitochondrial Ca²⁺ uniporter, MTP, mitochondrial transition pore, NCX_mito, mitochondrial Ca²⁺/Na⁺ exchanger, OMM, outer mitochondrial membrane, PKC, protein kinase C, RaM, rapid mode of mitochondrial Ca²⁺ uptake, RR, ruthenium red, SOCE, store-operated Ca²⁺ entry, UCP, uncoupling protein, VDAC, voltage-dependent anion selective channels

Keywords: Calcium signaling, ER Ca²⁺ release, grp75, IP₃ receptor, Letm1, mCa1, mCa2, MiCa, MCU, Mitochondrial Ca²⁺ uniporter, Mitofusin, p38MAPK, Uncoupling protein, UCP2/3