Temporal proteomics during neurogenesis reveals large-scale proteome and organelle remodeling via selective autophagy.

ABSTRACT: Cell state changes are associated with proteome remodeling to serve newly emergent cell functions. Here, we show that NGN2-driven conversion of human embryonic stem cells to induced neurons (iNeurons) is associated with increased PINK1-independent mitophagic flux that is temporally correlated with metabolic reprogramming to support oxidative phosphorylation. Global multiplex proteomics during neurogenesis revealed large-scale remodeling of functional modules linked with pluripotency, mitochondrial metabolism, and proteostasis. Differentiation-dependent mitophagic flux required BNIP3L and its LC3-interacting region (LIR) motif, and BNIP3L also promoted mitophagy in dopaminergic neurons. Proteomic analysis of ATG12^-/- iNeurons revealed accumulation of endoplasmic reticulum, Golgi,

SUBMITTER: Ordureau A 

PROVIDER: S-EPMC8688335 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature