Matrix AAA peptidase subunit paraplegin (SPG7)

Matrix AAA peptidase subunit paraplegin (SPG7) is a nuclear-encoded mitochondrial metalloprotease, localizing to the inner mitochondrial membrane as part of the m-AAA protease complex[1][2]. It functions as an ATP-dependent enzyme forming hexameric structures, coordinating membrane quality control via the degradation of misfolded/damaged mitochondrial proteins[1][2][7]. SPG7 is crucial for ribosome assembly within mitochondria and maintains bioenergetic stability by regulating mitochondrial membrane potential and reactive oxygen species[3][5]. It interacts with AFG3L2 and cyclophilin D, constituting an essential part of the mitochondrial permeability transition pore (PTP) complex, thereby controlling cell survival in response to Ca²⁺ and oxidative stress[4]. Pathogenic mutations in SPG7 cause hereditary spastic paraplegia type 7 and other neurodegenerative disorders and may impair mitochondrial DNA, leading to disease phenotypes ranging from muscle weakness and spasticity to increased risk of inflammation and atherosclerosis due to elevated free radical production[3][5][6]. Cyclosporine A inhibits PTP opening by disrupting SPG7-CypD interaction, providing a drug-targeting mechanism[4].

Other names

ParapleginSPG7Mitochondrial inner membrane m-AAA protease component parapleginCell matrix adhesion regulatorCMARCARPGNSPG5CSpastic paraplegia 7 proteinLOC101930112FLJ37308MGC126331

Inhibition of mitochondrial permeability transition pore by cyclosporine A through modulation of SPG7-CypD binding