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Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

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Neural Regeneration Research 2023年第5期18卷 1009-1016页

作者： marina g.yefimova Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of SciencesSt-PetersburgRussia Laboratoire STIM CNRS ERL 7003 Universitéde PoitiersPoitiersFrance

The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

关键词： autophagy Huntington’s disease Müller cells myelinosome-driven secretion myelinosomes ocular pathophysiology proteostasis retina retinal pigmented epithelium ubiquitin-proteasome system

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Autophagy is increased in cryptorchid testis resulting in abnormal spermatozoa

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Asian Journal of Andrology 2019年第6期21卷 570-576页

作者： marina g.yefimova Antoine Buschiazzo Agnes Burel Marie-Therese Lavault Celine Pimentel guilhem Jouve Sylvie Jaillard Bernard Jegou Nicolas Bourmeyster Celia Ravel Univ Rennes CHU RennesLaboratoire de Biologie de la Reproduction-CECOSInsermEH ESPIrset(Institut de recherche en santeenvironnement et travail)-UMR_S 1085Rennes F-35000France Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences194223 St-PetersburgRussia Univ Rennes Biosit Platform-MRICRennes 35000France Univ Rennes CHU RennesDepartment of Gynecology Obstetric and Human ReproductionRennes 35000France Univ Rennes CHU RennesDepartment of CytogeneticIrset(Institute for Environmental and Occupational Health)-UMR_S 1085Rennes 35000France Univ Rennes InsermEH ESPIrset(Institute for Environmental and Occupational Health)-UMR_S 1085Rennes F-35000France University of Poitiers-CHU Poitiers STIM ERL 7003 CNRSPoitiers 86021France

Autophagy is invoIved in spermatogenesis by regulating germ cell maturation.This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles.Cryptorchidism is associated with impairment of germ cell maturation revealed by the presence of immature forms of sperm cells in ejaculates.The aim of the present study was to evaluate the status of autophagy in sperm cells from cryptorchid patients.Semen samples of cryptorchid patients and normozoospermic controls were analyzed by immuno cytochemistry and electron microscopy.Autophagy protei ns,autophagy-related protein 9(ATg9)and microtubule-associated protein,lA/lB-light chain 3(LC3)were localized by immunocytochemistry on the acrosome and on the equatorial segment of sperm cells.LC3 was also detected in the midpiece of cryptorchid sperm tail.Autophagy substrate p62 protein was present in the acrosome and in the postequatorial segment of sperm in control samples,but not in the cryptorchid ones.Transmission electron microscopy revealed double-membrane-limited autophagosomes in postequatorial part of spermatozoa head and midpiece in cryptorchid samples.Partly degraded mitochondria were frequently discerned in autophagic vacuoles.In conclusion,autophagy is increased in sperm cells from patients with cryptorchid history comparatively to control.Our work provides insights into the role of autophagy in the maturation and survival of human male gametes in pathological conditions.Thus,regulating autophagy could represent a potential way to improve sperm quality in cryptorchid men.

关键词： autophagy cryptorchidism mitophagy spermatozoa

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