D'Amico 2019 Mol Cell
|D'Amico D, Mottis A, Potenza F, Sorrentino V, Li H, Romani M, Lemos V, Schoonjans K, Zamboni N, Knott G, Schneider BL, Auwerx J (2019) The RNA-binding protein PUM2 impairs mitochondrial dynamics and mitophagy during aging. Mol Cell [Epub ahead of print].|
Abstract: Little information is available about how post-transcriptional mechanisms regulate the aging process. Here, we show that the RNA-binding protein Pumilio2 (PUM2), which is a translation repressor, is induced upon aging and acts as a negative regulator of lifespan and mitochondrial homeostasis. Multi-omics and cross-species analyses of PUM2 function show that it inhibits the translation of the mRNA encoding for the mitochondrial fission factor (Mff), thereby impairing mitochondrial fission and mitophagy. This mechanism is conserved in C. elegans by the PUM2 ortholog PUF-8. puf-8 knock-down in old nematodes and Pum2 CRISPR/Cas9-mediated knockout in the muscles of elderly mice enhances mitochondrial fission and mitophagy in both models, hence improving mitochondrial quality control and tissue homeostasis. Our data reveal how a PUM2-mediated layer of post-transcriptional regulation links altered Mff translation to mitochondrial dynamics and mitophagy, thereby mediating age-related mitochondrial dysfunctions.
Copyright © 2018 Elsevier Inc. All rights reserved.
• Keywords: RNA binding proteins, Aging, Fission/fusion, Mitochondria, Mitochondrial dynamics, Mitophagy, Neurodegeneration, Protein aggregation diseases, Proteostasis, Ribonucleoprotein granules • Bioblast editor: Plangger M • O2k-Network Lab: CH Lausanne Auwerx J
Labels: MiParea: Respiration, Genetic knockout;overexpression Pathology: Aging;senescence
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Homogenate
Coupling state: OXPHOS Pathway: S, NS HRR: Oxygraph-2k