Patient-specific mutation of contact site protein Tomm70 causes neurodegeneration.

ABSTRACT: TOMM70 is a receptor at the contact site between mitochondria and the endoplasmic reticulum, and TOMM70 has been identified as a risk gene for hereditary spastic paraplegia. Furthermore, de novo missense variants of TOMM70 have been identified to cause neurological impairments in two unrelated patients. Here, we show that mutant zebrafish ruehreip25ca also harbour a missense mutation in tomm70, affecting the same conserved isoleucine residue as in one of the human patients. Using this model, we demonstrate how loss of Tomm70 function leads to impairment. At the molecular level, the mutation affected the interaction of Tomm70 with the endoplasmic reticulum protein Lam6, a known sterol transporter. At the neuronal level, the mutation impaired mitochondrial transport to the axons and dendrite

SUBMITTER: Garg V 

PROVIDER: S-EPMC12067081 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature