Biology subjects

Perez-Jimenez, M. M.

Publications and source records attributed to Perez-Jimenez, M. M..

3 recordsLinked to original sources

bioRxiv2019

Prohibitin depletion suppresses mitochondrial, lipogenic and autophagic defects of SGK-1 mutant extending lifespan; implication of autophagy and the UPRmt

Mitochondrial prohibitins (PHB) are highly conserved proteins with a peculiar effect on lifespan. While PHB depletion shortens lifespan of wild type animals, it enhances longevity of a plethora of metabolically compromised mutants, including target of rapamycin complex 2 (TORC2) mutants sgk-1 and rict-1. Here, we show that sgk-1 mutants have impaired mitochondrial homeostasis, lipogenesis, yolk formation and autophagy flux due to alterations in membrane lipid and sterol homeostasis. Remarkably, all these features are suppressed by PHB depletion. Lifespan analysis shows that autophagy and the mitochondrial unfolded protein response (UPRmt), but not mitophagy, are required for the enhanced longevity caused by PHB depletion in sgk-1 mutants. We hypothesize that UPRmt induction upon PHB depletion extends lifespan of sgk-1 mutants through autophagy. Our results strongly suggest that PHB depletion suppresses the autophagy defects of sgk-1 mutants by altering membrane lipid composition at ER-mitochondria contact sites, where TORC2 localizes.

cell biology↗

bioRxiv2019

Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

Aging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity by a still not fully understood mechanism. We find that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones and increases longevity. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) and is not additive to the longevity of germline-less mutants. Noteworthy, sul-2 mutations do not affect fertility. Thus, STS inactivation affects the germline signalling process regulating longevity. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of germline longevity by environmental cues. We also demonstrate that treatment with the specific STS inhibitor STX64, reproduces the longevity phenotype of sul-2 mutants. Remarkably, STS inhibition by either mutation or drug treatment ameliorates protein aggregation diseases in C. elegans models of Parkinson, Huntington and Alzheimer, as well as Alzheimer disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors for the treatment of aging and aging related diseases.

developmental biology↗

bioRxiv2018

Wolbachia control stem cell behavior and stimulate germline proliferation in filarial nematodes

Although symbiotic interactions are ubiquitous in the living world, examples of developmental symbioses are still scarce. We show here the crucial role of Wolbachia in the oogenesis of filarial nematodes, a class of parasites of biomedical and veterinary relevance. While the Wolbachia-depleted nematodes produce faulty embryos, we identified thanks to newly generated techniques the earliest requirements of Wolbachia in the germline. They stimulate its proliferation in a cell-autonomous manner, in parallel of the known key controllers, and not through nucleotide supplementation as previously hypothesized. We also found Wolbachia to maintain the quiescence of a pool of germline stem cells ensuring for many years a constant delivery of about 1400 eggs per day. The loss of quiescence upon Wolbachia depletion, as well as the disorganization of the distal germline suggest that Wolbachia are required to execute the proper germline stem cell developmental program in order to produce viable eggs and embryos.

developmental biology↗