Characterization of survival and stress resistance in S. cerevisiae mutants affected in peroxisome inheritance and proliferation, Δinp1 and Δpex11

  • Christian Q. ScheckhuberEmail author
Short Communication


Baker’s yeast is a valuable model system for the study of biological aging as it can be utilized for the measurement of replicative and chronological life spans in response to interventions. Whereas replicative aging in Saccharomyces cerevisiae mirrors dividing mammalian cells, chronological aging is seen in non-dividing cells. Aging is strongly influenced by the cellular organelles, especially by mitochondria which house essential functions like oxidative phosphorylation. Additionally, peroxisomes were shown to modulate the aging process, mainly by their turnover of reactive oxygen species. There is a fundamental interest in understanding how mitochondria and peroxisomes contribute to cellular aging. This work analyzes chronological aging in yeast mutants that are affected in peroxisomal proliferation and inheritance. Deletion of INP1 (retention of peroxisomes in the mother cell) or PEX11 (division of peroxisomes) leads to clearly reduced life spans compared to the wild-type control under conditions which depend on peroxisomal metabolism. Δinp1 cells are long-lived in contrast to the wild type and Δpex11 when assayed under conditions that not necessitate peroxisome function. Neither treatment affects the index of respiratory capacity, indicating fully functional mitochondria. Evaluation of stress resistances reveals that Δinp1 has significantly higher resistance to the apoptosis elicitor acetic acid. Old Δpex11 cells from an oleate culture are more susceptible to hydrogen peroxide treatment compared to Δinp1 and the wild type. Finally, aged cells are hyper-sensitive to heat shock treatment in contrast to young cells.


Funding information

This work was financially supported by CINVESTAV, Mexico.

Compliance with ethical standards

Competing interests

The author declares that he has no competing interests.


  1. Bernhardt D, Hamann A, Osiewacz HD (2014) The role of mitochondria in fungal aging. Curr Opin Microbiol 22:1–7CrossRefGoogle Scholar
  2. Boy-Marcotte E, Lagniel G, Perrot M, Bussereau F, Boudsocq A, Jacquet M, Labarre J (1999) The heat shock response in yeast: differential regulations and contributions of the Msn2p/Msn4p and Hsf1p regulons. Mol Microbiol 33:274–283CrossRefGoogle Scholar
  3. Brachmann CB, Davies A, Cost GJ, Caputo E, Li J, Hieter P, Boeke JD (1998) Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14:115–132CrossRefGoogle Scholar
  4. Breitenbach M, Laun P, Dickinson JR, Klocker A, Rinnerthaler M, Dawes IW, Aung-Htut MT, Breitenbach-Koller L, Caballero A, Nyström T, Büttner S, Eisenberg T, Madeo F, Ralser M (2012) The role of mitochondria in the aging processes of yeast. Subcell Biochem 57:55–78CrossRefGoogle Scholar
  5. Deori NM, Kale A, Maurya PK, Nagotu S (2018) Peroxisomes: role in cellular ageing and age related disorders. Biogerontology 19:303–324CrossRefGoogle Scholar
  6. Erdmann R, Blobel G (1995) Giant peroxisomes in oleic acid-inducedSaccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p. J Cell Biol 128:509–523CrossRefGoogle Scholar
  7. Erjavec N, Larsson L, Grantham J, Nyström T (2007) Accelerated aging and failure to segregate damaged proteins in Sir2 mutants can be suppressed by overproducing the protein aggregation-remodeling factor Hsp104p. Genes Dev 21:2410–2421CrossRefGoogle Scholar
  8. Fagarasanu A, Fagarasanu M, Eitzen GA, Aitchison JD, Rachubinski RA (2006) The peroxisomal membrane protein Inp2p is the peroxisome-specific receptor for the myosin V motor Myo2p of Saccharomyces cerevisiae. Dev Cell 10:587–600CrossRefGoogle Scholar
  9. Fagarasanu M, Fagarasanu A, Tam YY, Aitchison JD, Rachubinski RA (2005) Inp1p is a peroxisomal membrane protein required for peroxisome inheritance in Saccharomyces cerevisiae. J Cell Biol 169:765–775CrossRefGoogle Scholar
  10. Goldberg AA, Richard VR, Kyryakov P, Bourque SD, Beach A, Burstein MT, Glebov A, Koupaki O, Boukh-Viner T, Gregg C, Juneau M, English AM, Thomas DY, Titorenko VI (2010) Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes. Aging (Albany NY) 2:393–414CrossRefGoogle Scholar
  11. Hill SM, Hao X, Liu B, Nyström T (2014)Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae. Science 344:1389–1392CrossRefGoogle Scholar
  12. Jungwirth H, Ring J, Mayer T, Schauer A, Büttner S, Eisenberg T, Carmona-Gutierrez D, Kuchler K, Madeo F (2008) Loss of peroxisome function triggers necrosis. FEBS Lett 582:2882–2886CrossRefGoogle Scholar
  13. Kaeberlein M (2010) Lessons on longevity from budding yeast. Nature 464:513–519CrossRefGoogle Scholar
  14. Knoblach B, Sun X, Coquelle N, Fagarasanu A, Poirier RL, Rachubinski RA (2013) An ER-peroxisome tether exerts peroxisome population control in yeast. EMBO J 32:2439–2453CrossRefGoogle Scholar
  15. Krikken AM, Veenhuis M, van der Klei I (2009)Hansenula polymorpha pex11 cells are affected in peroxisome retention. FEBS J 276:1429–1439CrossRefGoogle Scholar
  16. Kumar S, de Boer R, van der Klei I (2018) Yeast cells contain a heterogeneous population of peroxisomes that segregate asymmetrically during cell division. J Cell Sci 131:jcs207522CrossRefGoogle Scholar
  17. Lee RE, Brunette S, Puente LG, Megeney LA (2010) Metacaspase Yca1 is required for clearance of insoluble protein aggregates. Proc Natl Acad Sci U S A 107:13348–13353CrossRefGoogle Scholar
  18. Lefevre SD, Kumar S, van der Klei I (2015) Inhibition of peroxisome fission, but not mitochondrial fission, increases yeast chronological lifespan. Cell Cycle 14:1698–1703CrossRefGoogle Scholar
  19. Lefevre SD, van Roermund CW, Wanders RJ, Veenhuis M, van der Klei I (2013) The significance of peroxisome function in chronological aging of Saccharomyces cerevisiae. Aging Cell 12:784–793CrossRefGoogle Scholar
  20. Ludovico P, Rodrigues F, Almeida A, Silva MT, Barrientos A, Corte-Real M (2002) Cytochrome c release and mitochondria involvement in programmed cell death induced by acetic acid in Saccharomyces cerevisiae. Mol Biol Cell 13:2598–2606CrossRefGoogle Scholar
  21. Manivannan S, Scheckhuber CQ, Veenhuis M, van der Klei I (2012) The impact of peroxisomes on cellular aging and death. Front Oncol 2:50CrossRefGoogle Scholar
  22. Manzanares-Estreder S, Espi-Bardisa J, Alarcón B, Pascual-Ahuir A, Proft M (2017) Multilayered control of peroxisomal activity upon salt stress in Saccharomyces cerevisiae. Mol Microbiol 104:851–868CrossRefGoogle Scholar
  23. Marshall PA, Krimkevich YI, Lark RH, Dyer JM, Veenhuis M, Goodman JM (1995) Pmp27 promotes peroxisomal proliferation. J Cell Biol 129:345–355CrossRefGoogle Scholar
  24. Mattiazzi Usaj M, Brloznik M, Kaferle P, Zitnik M, Wolinski H, Leitner F, Kohlwein SD, Zupan B, Petrovic U (2015)Genome-wide localization study of yeast Pex11 identifies peroxisome-mitochondria interactions through the ERMES complex. J Mol Biol 427:2072–2087CrossRefGoogle Scholar
  25. Munck JM, Motley AM, Nuttall JM, Hettema EH (2009) A dual function for Pex3p in peroxisome formation and inheritance. J Cell Biol 187:463–471CrossRefGoogle Scholar
  26. Opalinski L, Kiel JA, Williams C, Veenhuis M, van der Klei I (2011) Membrane curvature during peroxisome fission requires Pex11. EMBO J 30:5–16CrossRefGoogle Scholar
  27. Palermo V, Falcone C, Mazzoni C (2007) Apoptosis and aging in mitochondrial morphology mutants of S. cerevisiae. Folia Microbiol (Praha) 52:479–483CrossRefGoogle Scholar
  28. Saarikangas J, Barral Y (2015) Protein aggregates are associated with replicative aging without compromising protein quality control. Elife 4:e06197CrossRefGoogle Scholar
  29. Shoemaker DD, Lashkari DA, Morris D, Mittmann M, Davis RW (1996) Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar-coding strategy. Nat Genet 14:450–456CrossRefGoogle Scholar
  30. Sibirny AA (2016) Yeast peroxisomes: structure, functions and biotechnological opportunities. FEMS Yeast Res 16:fow038CrossRefGoogle Scholar
  31. Su J, Thomas AS, Grabietz T, Landgraf C, Volkmer R, Marrink SJ, Williams C, Melo MN (2018) The N-terminal amphipathic helix of Pex11p self-interacts to induce membrane remodelling during peroxisome fission. Biochim Biophys Acta Biomembr 1860:1292–1300CrossRefGoogle Scholar
  32. Titorenko VI, Terlecky SR (2011) Peroxisome metabolism and cellular aging. Traffic 12:252–259CrossRefGoogle Scholar
  33. Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344CrossRefGoogle Scholar
  34. van Dijken JP, Otto R, Harder W (1976) Growth of Hansenula polymorpha in a methanol-limited chemostat. Physiological responses due to the involvement of methanol oxidase as a key enzyme in methanol metabolism. Arch Microbiol 111:137–144CrossRefGoogle Scholar
  35. Veenhuis M, Kiel JA, van der Klei I (2003) Peroxisome assembly in yeast. Microsc Res Tech 61:139–150CrossRefGoogle Scholar
  36. Waterham HR, Ferdinandusse S, Wanders RJ (2016) Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta 1863:922–933CrossRefGoogle Scholar
  37. Williams C, Opalinski L, Landgraf C, Costello J, Schrader M, Krikken AM, Knoops K, Kram AM, Volkmer R, van der Klei I (2015) The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission. Proc Natl Acad Sci U S A 112:6377–6382CrossRefGoogle Scholar
  38. Yoshida Y, Niwa H, Honsho M, Itoyama A, Fujiki Y (2015) Pex11 mediates peroxisomal proliferation by promoting deformation of the lipid membrane. Biol Open 4:710–721CrossRefGoogle Scholar

Copyright information

© Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i. 2019

Authors and Affiliations

  1. 1.Centro de Investigación y de Estudios Avanzados del IPN - Unidad MonterreyApodacaMexico

Personalised recommendations