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Astaxanthin extends lifespan via altered biogenesis of the mitochondrial respiratory chain complex III

Ronit Hoffman, Laure D. Sultan, Ann Saada, Joseph Hirschberg, View ORCID ProfileOren Osterzetser-Biran, Yosef Gruenbaum
doi: https://doi.org/10.1101/698001
Ronit Hoffman
Dept. of Genetics, The Alexander Silberman Inst. of Life Sciences, Faculty of Mathematics and Natural Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel
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Laure D. Sultan
Dept. of Plant and Environmental Sciences, The Alexander Silberman Inst. of Life Sciences, Faculty of Mathematics and Natural Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
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Ann Saada
Department of Genetics and Metabolic Diseases, The Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Israel; Jerusalem 9112102, Israel.
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Joseph Hirschberg
Dept. of Genetics, The Alexander Silberman Inst. of Life Sciences, Faculty of Mathematics and Natural Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel
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Oren Osterzetser-Biran
Dept. of Plant and Environmental Sciences, The Alexander Silberman Inst. of Life Sciences, Faculty of Mathematics and Natural Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
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  • ORCID record for Oren Osterzetser-Biran
  • For correspondence: gru@vms.huji.ac.il oren.ostersetzer@mail.huji.ac.il
Yosef Gruenbaum
Dept. of Genetics, The Alexander Silberman Inst. of Life Sciences, Faculty of Mathematics and Natural Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel
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  • For correspondence: gru@vms.huji.ac.il oren.ostersetzer@mail.huji.ac.il
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Abstract

Astaxanthin is a keto-carotenoid produced in some bacteria and algae, which has very important industrial applications (i.e., in cosmetics, coloring additive in aquaculture and as a dietary supplement for human). Here, we analyzed the molecular basis of Astaxanthin-mediated prolongevity in the model organism, Caenorhabditis elegans. The increased lifespan effects of Astaxanthin are restricted in C. elegans to the adult phase and are uninfluenced by various other carotenoids tested. Genetic analyses indicated that the Astaxanthin-mediated life-extension relies on mitochondria activity, via the Rieske iron-sulfur polypeptide-1 (ISP-1), but is not influenced by the functions of other known longevity-related gene-loci, including CLK-1, DAF-2, DAT-16, EAT-2, GAS-1 GLP-1 or MEV-1. Biochemical analyses of native respiratory complexes showed that Astaxanthin affects the biogenesis of holo-complex III (and likely supercomplex I+III, as well). Effects on holo-CIII assembly and activity were also indicated by in-vitro assays, with mitochondria isolated from worms, rodents, human and plants, which were treated with Astaxanthin. These data indicated a cross-species effect on the oxidative phosphorylation (OXPHOS) machinery by the carotenoid, and provide with further insights into the molecular mechanism of animals longevity extension by Astaxanthin.

Significance Statement Astaxanthin is a widely consumed pigment by animals and human. In this study we find that Astaxanthin, but not other tested carotenoids, significantly extends the lifespan of animals by affecting respiratory complex III (CIII) biogenesis of the mitochondria, in plants, C. elegans, rodents and human. We further propose a model to try explaining this effect of astaxanthin on animals’ longevity.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 10, 2019.
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Astaxanthin extends lifespan via altered biogenesis of the mitochondrial respiratory chain complex III
Ronit Hoffman, Laure D. Sultan, Ann Saada, Joseph Hirschberg, Oren Osterzetser-Biran, Yosef Gruenbaum
bioRxiv 698001; doi: https://doi.org/10.1101/698001
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Astaxanthin extends lifespan via altered biogenesis of the mitochondrial respiratory chain complex III
Ronit Hoffman, Laure D. Sultan, Ann Saada, Joseph Hirschberg, Oren Osterzetser-Biran, Yosef Gruenbaum
bioRxiv 698001; doi: https://doi.org/10.1101/698001

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