A High-Content Screen Identifies TPP1 and Aurora B as Regulators of Axonal Mitochondrial Transport.

ABSTRACT: Dysregulated axonal trafficking of mitochondria is linked to neurodegenerative disorders. We report a high-content screen for small-molecule regulators of the axonal transport of mitochondria. Six compounds enhanced mitochondrial transport in the sub-micromolar range, acting via three cellular targets: F-actin, Tripeptidyl peptidase 1 (TPP1), or Aurora Kinase B (AurKB). Pharmacological inhibition or small hairpin RNA (shRNA) knockdown of each target promotes mitochondrial axonal transport in rat hippocampal neurons and induced pluripotent stem cell (iPSC)-derived human cortical neurons and enhances mitochondrial transport in iPSC-derived motor neurons from an amyotrophic lateral sclerosis (ALS) patient bearing one copy of SOD1^A4V mutation. Our work identifies druggable regulator

SUBMITTER: Shlevkov E 

PROVIDER: S-EPMC6937139 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature