RRC ID 76002
Author Lionaki E, Gkikas I, Daskalaki I, Ioannidi MK, Klapa MI, Tavernarakis N.
Title Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis.
Journal Nat Commun
Abstract Sustained mitochondrial fitness relies on coordinated biogenesis and clearance. Both processes are regulated by constant targeting of proteins into the organelle. Thus, mitochondrial protein import sets the pace for mitochondrial abundance and function. However, our understanding of mitochondrial protein translocation as a regulator of longevity remains enigmatic. Here, we targeted the main protein import translocases and assessed their contribution to mitochondrial abundance and organismal physiology. We find that reduction in cellular mitochondrial load through mitochondrial protein import system suppression, referred to as MitoMISS, elicits a distinct longevity paradigm. We show that MitoMISS triggers the mitochondrial unfolded protein response, orchestrating an adaptive reprogramming of metabolism. Glycolysis and de novo serine biosynthesis are causatively linked to longevity, whilst mitochondrial chaperone induction is dispensable for lifespan extension. Our findings extent the pro-longevity role of UPRmt and provide insight, relevant to the metabolic alterations that promote or undermine survival and longevity.
Volume 13(1)
Pages 651
Published 2022-2-3
DOI 10.1038/s41467-022-28272-1
PII 10.1038/s41467-022-28272-1
PMID 35115503
PMC PMC8814026
MeSH Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism Energy Metabolism / genetics Longevity / genetics Membrane Potential, Mitochondrial / genetics Metabolomics / methods Microscopy, Fluorescence Mitochondria / genetics Mitochondria / metabolism* Mitochondrial Precursor Protein Import Complex Proteins / genetics Mitochondrial Precursor Protein Import Complex Proteins / metabolism Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Protein Transport / genetics RNA Interference Reactive Oxygen Species / metabolism Serine / genetics Serine / metabolism* Survival Analysis
C.elegans tm4525 tm4803 tm3165