Unknown

Dataset Information

0

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, and mitochondria during differentiation, indicative of widespread organelle remodeling during neurogenesis. This work reveals broad organelle remodeling of membrane-bound organelles during NGN2-driven neurogenesis via autophagy, identifies BNIP3L's central role in programmed mitophagic flux, and provides a proteomic resource for elucidating how organelle remodeling and autophagy alter the proteome during changes in cell state.

SUBMITTER: Ordureau A 

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

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Ordureau Alban A   Kraus Felix F   Zhang Jiuchun J   An Heeseon H   Park Sookhee S   Ahfeldt Tim T   Paulo Joao A JA   Harper J Wade JW  

Molecular cell 20211025 24


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, mitochondri  ...[more]

Similar Datasets

2021-08-09 | MSV000087961 | MassIVE
2024-10-04 | GSE278059 | GEO
| S-EPMC7819763 | biostudies-literature
| PRJNA1165290 | ENA
| S-EPMC3861700 | biostudies-literature
2023-12-19 | PXD046440 | Pride
2020-10-09 | GSE154643 | GEO
| S-EPMC1458916 | biostudies-literature
| S-EPMC2637050 | biostudies-literature
| S-EPMC4052807 | biostudies-literature