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Identification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast

Author

Listed:
  • Cierra N. Sing

    (Columbia University
    Columbia University)

  • Enrique J. Garcia

    (Columbia University)

  • Thomas G. Lipkin

    (Columbia University
    University of California)

  • Thomas M. Huckaba

    (Columbia University
    Xavier University of Louisiana)

  • Catherine A. Tsang

    (Columbia University)

  • Arielle C. Coughlin

    (Columbia University)

  • Emily J. Yang

    (Columbia University)

  • Istvan R. Boldogh

    (Columbia University)

  • Ryo Higuchi-Sanabria

    (Columbia University
    Columbia University
    University of Southern California)

  • Liza A. Pon

    (Columbia University
    Columbia University)

Abstract

In yeast, actin cables are F-actin bundles that are essential for cell division through their function as tracks for cargo movement from mother to daughter cell. Actin cables also affect yeast lifespan by promoting transport and inheritance of higher-functioning mitochondria to daughter cells. Here, we report that actin cable stability declines with age. Our genome-wide screen for genes that affect actin cable stability identified the open reading frame YKL075C. Deletion of YKL075C results in increases in actin cable stability and abundance, mitochondrial fitness, and replicative lifespan. Transcriptome analysis revealed a role for YKL075C in regulating branched-chain amino acid (BCAA) metabolism. Consistent with this, modulation of BCAA metabolism or decreasing leucine levels promotes actin cable stability and function in mitochondrial quality control. Our studies support a role for actin stability in yeast lifespan, and demonstrate that this process is controlled by BCAA and a previously uncharacterized ORF YKL075C, which we refer to as actin, aging and nutrient modulator protein 1 (AAN1).

Suggested Citation

  • Cierra N. Sing & Enrique J. Garcia & Thomas G. Lipkin & Thomas M. Huckaba & Catherine A. Tsang & Arielle C. Coughlin & Emily J. Yang & Istvan R. Boldogh & Ryo Higuchi-Sanabria & Liza A. Pon, 2022. "Identification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30045-9
    DOI: 10.1038/s41467-022-30045-9
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    References listed on IDEAS

    as
    1. Wolfgang M. Pernice & Jason D. Vevea & Liza A. Pon, 2016. "A role for Mfb1p in region-specific anchorage of high-functioning mitochondria and lifespan in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    2. Adam L. Hughes & Daniel E. Gottschling, 2012. "An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast," Nature, Nature, vol. 492(7428), pages 261-265, December.
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