SPG7 targets the m-AAA protease complex to process MCU for uniporter assembly, Ca²⁺ influx, and regulation of mitochondrial permeability transition pore opening.

ABSTRACT: The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca²⁺-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca²⁺ concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca²⁺ uniporter complexes. We found that

SUBMITTER: Hurst S 

PROVIDER: S-EPMC6635443 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature