Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia.

ABSTRACT:

Background

Mutations of the mitochondrial protein paraplegin cause hereditary spastic paraplegia type 7 (SPG7), a so-far untreatable degenerative disease of the upper motoneuron with still undefined pathomechanism. The intermittent mitochondrial permeability transition pore (mPTP) opening, called flickering, is an essential process that operates to maintain mitochondrial homeostasis by reducing intra-matrix Ca²⁺ and reactive oxygen species (ROS) concentration, and is critical for efficient synaptic function.

Methods

We use a fluorescence-based approach to measure mPTP flickering in living cells and biochemical and molecular biology techniques to dissect the pathogenic mechanism of SPG7. In the SPG7 animal model we evaluate the potential improvement of the motor de

SUBMITTER: Sambri I 

PROVIDER: S-EPMC7553352 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature