Mitochondrial calcium transport during autophagy initiation

Abstract

While it has been shown that Ca²⁺ dynamics at the ER membrane is essential for the initiation of certain types of autophagy such as starvation-induced autophagy, how mitochondrial Ca²⁺ transport changes during the first stage of autophagy is not systemically characterized. An investigation of mitochondrial Ca²⁺ dynamics during autophagy initiation may help us determine the relationship between autophagy and mitochondrial Ca²⁺ fluxes. Here we examine acute mitochondrial and ER calcium responses to a panel of autophagy inducers in different cell types. Mitochondrial Ca²⁺ transport and Ca²⁺ transients at the ER membrane are triggered by different autophagy inducers. The mitophagy-inducer-initiated mitochondrial Ca²⁺ uptake relies on mitochondrial calcium uniporter and may decelerate the following mitophagy. In neurons derived from a Parkinson's patient, mitophagy-inducer-triggered mitochondrial Ca²⁺ influx is faster, which may slow the ensuing mitophagy.