Mitochondrial Calcium Transport During Autophagy Initiation

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.

ER Ca2+ transient; IP3R; MCU; Parkinson; RyR; autophagy; mitochondrial Ca2+ uptake; mitophagy.