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

Eirini Lionaki (), Ilias Gkikas, Ioanna Daskalaki, Maria-Konstantina Ioannidi, Maria I. Klapa and Nektarios Tavernarakis ()
Additional contact information
Eirini Lionaki: Foundation for Research and Technology — Hellas
Ilias Gkikas: Foundation for Research and Technology — Hellas
Ioanna Daskalaki: Foundation for Research and Technology — Hellas
Maria-Konstantina Ioannidi: Foundation for Research and Technology-Hellas (FORTH/ICE-HT)
Maria I. Klapa: Foundation for Research and Technology-Hellas (FORTH/ICE-HT)
Nektarios Tavernarakis: Foundation for Research and Technology — Hellas

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28272-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28272-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28272-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().