Mitochondrial Ca2+ signals in autophagy

• Published in: Cell calcium (Edinburgh) 2012-07, Vol.52 (1), p.44-51
• Main Authors: Cárdenas, César, Foskett, J. Kevin
• Format: Article
• Language: English
• Subjects: Advanced Basic Science
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2012.03.001

Abstract Macroautophagy (autophagy) is a lysosomal degradation pathway that is conserved from yeast to humans that plays an important role in recycling cellular constituents in all cells. A number of protein complexes and signaling pathways impinge on the regulation of autophagy, with the mammalian target of rapamycin (mTOR) as the central player in the canonical pathway. Cytoplasmic Ca2+ signaling also regulates autophagy, with both activating and inhibitory effects, mediated by the canonical as well as non-canonical pathways. Here we review this regulation, with a focus on the role of an mTOR-independent pathway that involves the inositol trisphosphate receptor (InsP3 R) Ca2+ release channel and Ca2+ signaling to mitochondria. Constitutive InsP3 R Ca2+ transfer to mitochondria is required for autophagy suppression in cells in nutrient-replete media. In its absence, cells become metabolically compromised due to insufficient production of reducing equivalents to support oxidative phosphorylation. Absence of this Ca2+ transfer to mitochondria results in activation of AMPK, which activates mTOR-independent pro-survival autophagy. Constitutive InsP3 R Ca2+ release to mitochondria is an essential cellular process that is required for efficient mitochondrial respiration, maintenance of normal cell bioenergetics and suppression of autophagy.