PXD024180

PXD024180 is an original dataset announced via ProteomeXchange.

Title	Discovering the novel role of the S-adenosyl methionine synthetase SAMS-1 in mediating mitochondrial homeostasis during aging
Description	Current worldwide demographics came to the point of the prevalence of people of middle age when the majority of age-related disease start to occur. The existing strategies (dietary and pharmacological interventions) are mostly tested or include treatment starting from young age to promote healthy aging and do not consider altered metabolism, and mitochondrial malfunction at late life onset. With age, mitochondria are characterized by its compromised ability to maintain tubular integral mitochondrial network in cells and to provide essential level of metabolites, altogether leading to an emergence of age-associated diseases. Therefore finding the solution for improved plasticity of mitochondria during aging is fundament and of high importance. In this work, I searched for molecular adaptations that counteract mitochondrial defects systemically during aging using Caenorhabditis elegans as a genetic model system. With this purpose, I addressed paradox worms, clk-1(qm30) and isp-1(qm150), which were discovered by S. Hekimi group as the first long-lived organisms with hypomorphic mutations in electron transport chain of mitochondria. Using longitudinal and comparative whole proteome analysis, I observed age-associated decline of SAMS-1, an enzyme converting methionine into S-adenosyl methionine (SAM) within one-carbon metabolism pathway in the cell. Remarkably, both long-lived mitochondrial mutants express an elevated level of SAMS-1 compared to wild type during aging. Moreover, sams-1 RNAi-mediated knockdown (sams-1 KD) abrogated the extended longevity of mitochondrial mutants, but not wild type animals. I uncovered, that sams-1 KD promotes mitochondrial fragmentation and HSP-6 promoter expression, a marker of mitochondrial unfolded stress response, mtUPR, at young age. I showed that lifetime SAM supplementation restored a fraction of tubular mitochondria in sams-1 KD worms at post-reproductive age. I discovered, that SAM regulates mitochondrial morphology and mtUPR through the PMT-1-mediated pathway for synthesis of phosphatidylcholine, one of key lipid components of cellular membranes. Altogether, I deciphered, that SAMS-1 is a molecular switch controlling mitochondrial homeostasis during aging, and its enzymatic end-product SAM represents a promising natural intervention for a balanced mitochondrial plasticity at post-reproductive age. The future follow up study will show if SAM supplementation can improve mitochondrial function at old age and extend lifespan.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-23_11:10:40.181.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emilio Cirri
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: NEWT:6239;
ModificationList	carbamoylated residue; monohydroxylated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-15 03:42:16	ID requested
⏵ 1	2026-02-23 11:10:40	announced

Dataset with its publication pending

submitter keyword: Mitochondria,Aging

Maria Ermolaeva
contact affiliation	Leibniz Institute for Aging - Fritz-Lipmann-Institut (FLI) Beutenbergstraße 11 07745 Jena
contact email	maria.ermolaeva@leibniz-fli.de
lab head
Emilio Cirri
contact affiliation	Leibniz Institute on Ageing Fritz Lipmann Institute Jena
contact email	emilio.cirri@fli-leibniz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024180
     1. Label: PRIDE project
     2. Name: Discovering the novel role of the S-adenosyl methionine synthetase SAMS-1 in mediating mitochondrial homeostasis during aging