Work

Genetic manipulation of SPG7 or NipSnap2 does not affect mitochondrial permeability transition

Year: 2020

Type: article

Abstract: Opening of the mitochondrial permeability transition (MPT) pore is known to mediate cellular necrosis in response to a number of toxic stimuli, such as elevated Ca 2+ levels and oxidative stress, and therefore contributes to multiple pathologies 1 . However, the identity of the components that make up the channel-forming unit of the MPT pore remain uncertain, with many candidates being ruled out by genetic studies 2 , 3 , and only cyclophilin-D (CypD) confirmed as a key regulator of the MPT pore 2 , 3 . A previous study identified the mitochondrial AAA-protease subunit spastic paraplegia 7 (SPG7) as a novel modulator of the MPT pore 4 . They reported that SPG7 interacted with CypD and that depletion of SPG7 in HEK-293 cells greatly attenuated Ca 2+ and oxidative stress-induced MPT and cell death. The authors concluded that SPG7 was an essential component of the MPT pore. They additionally reported that depletion of NipSnap2 (also known as Gbas), a mitochondrial protein of unknown function, also attenuated MPT. The latter was interesting, Halestrap’s group have also identified NipSnap2 as a CypD-binding protein 5 .

Source: Cell Death Discovery

DOI: 10.1038/s41420-020-0239-6

Authors: Paula J. Klutho, Ryan J. Dashek, Lihui Song, Christopher P. Baines

Institution: University of Missouri

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,870