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Quercetin-Induced Lifespan Extension in Podospora anserina Requires Methylation of the Flavonoid by the O-Methyltransferase PaMTH1.

ABSTRACT: Quercetin is a flavonoid that is ubiquitously found in vegetables and fruits. Like other flavonoids, it is active in balancing cellular reactive oxygen species (ROS) levels and has a cyto-protective function. Previously, a link between ROS balancing, aging, and the activity of O-methyltransferases was reported in different organisms including the aging model Podospora anserina. Here we describe a role of the S-adenosylmethionine-dependent O-methyltransferase PaMTH1 in quercetin-induced lifespan extension. We found that effects of quercetin treatment depend on the methylation state of the flavonoid. Specifically, we observed that quercetin treatment increases the lifespan of the wild type but not of the PaMth1 deletion mutant. The lifespan increasing effect is not associated with effects of quercetin on mitochondrial respiration or ROS levels but linked to the induction of the PaMth1 gene. Overall, our data demonstrate a novel role of O-methyltransferase in quercetin-induced longevity and identify the underlying pathway as part of a network of longevity assurance pathways with the perspective to intervene into mechanisms of biological aging.

SUBMITTER: Warnsmann V

PROVIDER: S-EPMC5945814 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Quercetin-Induced Lifespan Extension in Podospora anserina Requires Methylation of the Flavonoid by the O-Methyltransferase PaMTH1.

Warnsmann Verena V Hainbuch Saskia S Osiewacz Heinz D HD

Frontiers in genetics 20180504

Quercetin is a flavonoid that is ubiquitously found in vegetables and fruits. Like other flavonoids, it is active in balancing cellular reactive oxygen species (ROS) levels and has a cyto-protective function. Previously, a link between ROS balancing, aging, and the activity of O-methyltransferases was reported in different organisms including the aging model Podospora anserina. Here we describe a role of the S-adenosylmethionine-dependent O-methyltransferase PaMTH1 in ...[more]

PMID: 29780405

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Project description:The endoplasmic reticulum (ER) is an elaborate organelle composed of distinct structural and functional domains. ER structure and dynamics involve membrane-shaping proteins of the reticulon and Yop1/DP1 families, which promote membrane curvature and regulate ER shaping and remodeling. Here, we analyzed the function of the reticulon (RTN1) and Yop1 proteins (YOP1 and YOP2) of the model fungus Podospora anserina and their contribution to sexual development. We found that RTN1 and YOP2 localize to the peripheral ER and are enriched in the dynamic apical ER domains of the polarized growing hyphal region. We discovered that the formation of these domains is diminished in the absence of RTN1 or YOP2 and abolished in the absence of YOP1 and that hyphal growth is moderately reduced when YOP1 is deleted in combination with RTN1 and/or YOP2. In addition, we found that RTN1 associates with the Spitzenkörper. Moreover, RTN1 localization is regulated during meiotic development, where it accumulates at the apex of growing asci (meiocytes) during their differentiation and at their middle region during the subsequent meiotic progression. Furthermore, we discovered that loss of RTN1 affects ascospore (meiotic spore) formation, in a process that does not involve YOP1 or YOP2. Finally, we show that the defects in ascospore formation of rtn1 mutants are associated with defective nuclear segregation and spindle dynamics throughout meiotic development. Our results show that sexual development in P. anserina involves a developmental remodeling of the ER that implicates the reticulon RTN1, which is required for meiotic nucleus segregation. IMPORTANCE Meiosis consists of a reductional cell division, which allows ploidy maintenance during sexual reproduction and which provides the potential for genetic recombination, producing genetic variation. Meiosis constitutes a process of foremost importance for eukaryotic evolution. Proper partitioning of nuclei during this process relies on accurate functioning and positioning of the spindle, the microtubule cytoskeletal apparatus that conducts chromosome segregation. In this research, we show that in the model fungus Podospora anserina this process requires a protein involved in structuring the endoplasmic reticulum (ER)-the reticulon RTN1. The ER is a complex organelle composed of distinct structural domains, including different peripheral domains and the nuclear envelope. Our findings suggest that spindle dynamics during meiosis relies on remodeling of the ER membrane, which involves the activity of RTN1. Our research discloses that the proteins implicated in shaping the ER are main contributors to the regulation of nuclear dynamics during the sexual cycle.

Dataset Information

Quercetin-Induced Lifespan Extension in Podospora anserina Requires Methylation of the Flavonoid by the O-Methyltransferase PaMTH1.

Publications

Quercetin-Induced Lifespan Extension in <i>Podospora anserina</i> Requires Methylation of the Flavonoid by the <i>O</i>-Methyltransferase PaMTH1.

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