Mitochondrial Ca2+ signals in autophagy

作者：Cardenas Cesar; Foskett J Kevin^*

来源：Cell Calcium, 2012, 52(1): 44-51.

DOI：10.1016/j.ceca.2012.03.001

• Inositol trisphosphate receptor
• Calcium
• Mitochondria
• Endoplasmic reticulum
• Ion channel
• Bioenergetics
• ATP
• Bcl-2
• Bcl-x(L)
• Macroautophagy
• mTOR
• AMP kinase
• AMPK
• CaMKK beta
• Lithium
• DT40
• Xestospongin
• MCU
• Uniporter
• Calpain

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 (InsP(3)R) Ca2+ release channel and Ca2+ signaling to mitochondria. Constitutive InsP(3)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 prosurvival autophagy. Constitutive InsP(3)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.

• 出版日期2012-7