Aggregation-prone Tau impairs mitochondrial import, which affects organelle morphology and neuronal complexity.

ABSTRACT: Mitochondrial protein import is essential for organellar biogenesis, and thereby for the sufficient supply of cytosolic ATP - which is particularly important for cells with high energy demands like neurons. This study explores the prospect of import machinery perturbation as a cause of neurodegeneration instigated by the accumulation of aggregating proteins linked to disease. We found that the aggregation-prone Tau variant (TauP301L) reduces the levels of components of the import machinery of the outer (TOM20, encoded by TOMM20) and inner membrane (TIM23, encoded by TIMM23) while associating with TOM40 (TOMM40). Intriguingly, this interaction affects mitochondrial morphology, but not protein import or respiratory function; raising the prospect of an intrinsic rescue mechanism. Indeed, TauP

SUBMITTER: Needs HI 

PROVIDER: S-EPMC10357015 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature