Regulation of Endoplasmic Reticulum-Mitochondria Tethering and Ca²⁺ Fluxes by TDP-43 via GSK3β.

ABSTRACT: Mitochondria-ER contacts (MERCs), tightly regulated by numerous tethering proteins that act as molecular and functional connections between the two organelles, are essential to maintain a variety of cellular functions. Such contacts are often compromised in the early stages of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). TDP-43, a nuclear protein mainly involved in RNA metabolism, has been repeatedly associated with ALS pathogenesis and other neurodegenerative diseases. Although TDP-43 neuropathological mechanisms are still unclear, the accumulation of the protein in cytoplasmic inclusions may underlie a protein loss-of-function effect. Accordingly, we investigated the impact of siRNA-mediated TDP-43 silencing on MERCs and the related cellular parameters

SUBMITTER: Peggion C 

PROVIDER: S-EPMC8584823 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature