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Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis

Lionaki, Eirini, Gkikas, Ilias, Daskalaki, Ioanna, Ioannidi, Maria-Konstantina, Klapa, Maria I., Tavernarakis, Nektarios·2022·Nature Communications
DOI 10.1038/s41467-022-28272-1PMC PMC8814026
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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 UPR mt and provide insight, relevant to the metabolic alterations that promote or undermine survival and longevity.

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  • In C. elegans, partial inhibition of mitochondrial protein synthesis or import enhances lifespan through a mechanism involving the mitochondrial unfolded protein response.

    “In C. elegans , partial inhibition of mitochondrial protein synthesis or import enhances lifespan through a mechanism involving the mitochondrial unfolded protein response (UPR mt ) 163 .”

    From Hallmarks of aging: An expanding universe (2023) · cites this paper as [163]

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Metadata

Authors
Lionaki, E., Gkikas, I., Daskalaki, I., Ioannidi, M.-K., Klapa, M. I., & Tavernarakis, N.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-02-03
Volume
13
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-022-28272-1
PMC
PMC8814026
Cited by
56
References
17
Language
en
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