title: High- and low-calcium-dependent mechanisms of mitochondrial calcium signalling.
abstract: The Ca(2+) coupling between endoplasmic reticulum (ER) and mitochondria is central to multiple cell survival and cell death mechanisms. Cytoplasmic [Ca(2+)] ([Ca(2+)](c)) spikes and oscillations produced by ER Ca(2+) release are effectively delivered to the mitochondria. Propagation of [Ca(2+)](c) signals to the mitochondria requires the passage of Ca(2+) across three membranes, namely the ER membrane, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM). Strategic positioning of the mitochondria by cytoskeletal transport and interorganellar tethers provides a means to promote the local transfer of Ca(2+) between the ER membrane and OMM. In this setting, even >100 microM [Ca(2+)] may be attained to activate the low affinity mitochondrial Ca(2+) uptake. However, a mitochondrial [Ca(2+)] rise has also been documented during submicromolar [Ca(2+)](c) elevations. Evidence has been emerging that Ca(2+) exerts allosteric control on the Ca(2+) transport sites at each membrane, providing mechanisms that may facilitate the Ca(2+) delivery to the mitochondria. Here we discuss the fundamental mechanisms of ER and mitochondrial Ca(2+) transport, particularly the control of their activity by Ca(2+) and evaluate both high- and low-[Ca(2+)]-activated mitochondrial calcium signals in the context of cell physiology.
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary. spat@puskin.sote.hu
authors.forename: András
authors.initials: A
authors.lastname: Spät
authors.forename: Gergo
authors.initials: G
authors.lastname: Szanda
authors.forename: György
authors.initials: G
authors.lastname: Csordás
authors.forename: György
authors.initials: G
authors.lastname: Hajnóczky
mesh_terms: D000494:Allosteric Regulation / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium