Bax

https://www.life-science-alliance.org/content/3/5/e201900527

https://www.ncbi.nlm.nih.gov/pubmed/32245838?dopt=Abstract

Defective nucleotide-dependent assembly and membrane fusion in Mfn2 CMT2A variants improved by Bax.

Life Sci Alliance. 2020 May;3(5):

Authors: Samanas NB, Engelhart EA, Hoppins S

Abstract

Mitofusins are members of the dynamin-related protein family of large GTPases that harness the energy from nucleotide hydrolysis to remodel membranes. Mitofusins possess four structural domains, including a GTPase domain, two extended helical bundles (HB1 and HB2), and a transmembrane region. We have characterized four Charcot-Marie-Tooth type 2A-associated variants with amino acid substitutions in Mfn2 that are proximal to the hinge that connects HB1 and HB2. A functional defect was not apparent in cells as the mitochondrial morphology of Mfn2-null cells was restored by expression of any of these variants. However, a significant fusion deficiency was observed in vitro, which was improved by the addition of crude cytosol extract or soluble Bax. All four variants had reduced nucleotide-dependent assembly in cis, but not trans, and this was also improved by the addition of Bax. Together, our data demonstrate an important role for this region in Mfn2 GTP-dependent oligomerization and membrane fusion and is consistent with a model where cytosolic factors such as Bax are masking molecular defects associated with Mfn2 disease variants in cells.

PMID: 32245838 [PubMed – as supplied by publisher]

PubMed:32245838

Samanas NB, Engelhart EA, Hoppins S