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Peer-reviewedCC BYNature communications

A role for selective ER autophagy in gametogenic rejuvenation revealed by high-throughput lifespan profiling.

  • Silvan Spiri1
  • Tina Lynn Sing2
  • Nhi Phung2
  • Jay S Goodman2
  • Elçin Ünal3,4,5
  • Gloria Ann Brar6,7,8
8 affiliations
  1. 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
  2. 2Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  3. 3Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
  4. 4California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA. [email protected].
  5. 5Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
  6. 6Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
  7. 7California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA. [email protected].
  8. 8Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
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Abstract

During mitotic growth, Saccharomyces cerevisiae cells age by dividing asymmetrically, producing young daughter cells while retaining age-associated damage in the mother cell, which will eventually become senescent. Gametogenesis naturally and fully resets precursor cell lifespan, even for replicatively aged cells. However, the mechanisms responsible for gametogenic rejuvenation have remained mysterious. This is partly due to the existing methods to quantify lifespan resetting in this context, which are limited to low-throughput and labor-intensive approaches. Here, we introduce a high-throughput assay that allows systematic characterization of factors required for gametogenic rejuvenation. With this approach, we show that we can sensitively measure a wide range of gamete replicative lifespans that are consistent with established mutants. Excitingly, we also discover that Atg39 and Atg40, receptors involved in selective autophagy of the ER, are molecular determinants of gametogenic rejuvenation. This technique will enable systematic identification of the molecular factors that drive gametogenic rejuvenation.

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Cite

BibTeXRIS
BibTeX
@article{spiri2026role,
  title = {{A role for selective ER autophagy in gametogenic rejuvenation revealed by high-throughput lifespan profiling.}},
  author = {Silvan Spiri and Tina Lynn Sing and Nhi Phung and Jay S Goodman and Elçin Ünal and Gloria Ann Brar},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77993-0},
  url = {https://europepmc.org/article/MED/42957684},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A role for selective ER autophagy in gametogenic rejuvenation revealed by high-throughput lifespan profiling.
AU  - Silvan Spiri
AU  - Tina Lynn Sing
AU  - Nhi Phung
AU  - Jay S Goodman
AU  - Elçin Ünal
AU  - Gloria Ann Brar
PY  - 2026
DA  - 2026/09/29
JO  - Nature communications
DO  - 10.1038/s41467-026-77993-0
UR  - https://europepmc.org/article/MED/42957684
AB  - During mitotic growth, Saccharomyces cerevisiae cells age by dividing asymmetrically, producing young daughter cells while retaining age-associated damage in the mother cell, which will eventually become senescent. Gametogenesis naturally and fully resets precursor cell lifespan, even for replicatively aged cells. However, the mechanisms responsible for gametogenic rejuvenation have remained mysterious. This is partly due to the existing methods to quantify lifespan resetting in this context, which are limited to low-throughput and labor-intensive approaches. Here, we introduce a high-throughput assay that allows systematic characterization of factors required for gametogenic rejuvenation. With this approach, we show that we can sensitively measure a wide range of gamete replicative lifespans that are consistent with established mutants. Excitingly, we also discover that Atg39 and Atg40, receptors involved in selective autophagy of the ER, are molecular determinants of gametogenic rejuvenation. This technique will enable systematic identification of the molecular factors that drive gametogenic rejuvenation.
SN  - 2041-1723
ER  -