Spastic paraplegia 7 (Paraplegin) (SPG7)

Spastic paraplegia 7 (SPG7), also known as paraplegin, is a mitochondrial inner membrane protein that functions as a catalytic subunit of the m-AAA protease complex. In 2015, it was identified as a novel and essential component of the mitochondrial permeability transition pore (mPTP), a high-conductance channel whose opening leads to mitochondrial swelling, membrane potential dissipation, and cell death [3.1.1, 3.1.2]. SPG7 interacts with Cyclophilin D (CypD) and VDAC to facilitate pore opening in response to calcium overload and oxidative stress [3.1.1, 3.1.5]. Mutations in the SPG7 gene are the primary cause of hereditary spastic paraplegia type 7, a neurodegenerative disorder characterized by progressive spasticity and weakness of the lower limbs [2.3.3, 2.3.4]. While SPG7 is a potential therapeutic target for conditions involving excessive mPTP opening, such as ischemia-reperfusion injury, its role in maintaining mitochondrial proteostasis presents a significant challenge for drug development, as its loss can lead to severe mitochondrial dysfunction [3.1.4, 3.3.1].

Other names

ParapleginPGNCARCMARm-AAA protease subunit SPG7

SPG7 forms a heterooligomeric complex with VDAC and Cyclophilin D (CypD) at the inner/outer mitochondrial membrane contact sites to facilitate the opening of the mPTP in response to calcium and ROS [3.1.1, 3.1.2].