Autor según el artículo: Vazquez-Martin A, Van den Haute C, Cufí S, Corominas-Faja B, Cuyàs E, Lopez-Bonet E, Rodriguez-Gallego E, Fernández-Arroyo S, Joven J, Baekelandt V, Menendez JA.
Departamento: Bioquímica i Biotecnologia Medicina i Cirurgia
Autor/es de la URV: FERNANDEZ ARROYO, SALVADOR / Joven Maried, Jorge / Rodríguez Gallego, Esther
Palabras clave: Stem cells Pluripotency Mitophagy Mitochondria Epigenetics Cancer pluripotency mitophagy mitochondria epigenetics cancer
Resumen: Our understanding on how selective mitochondrial autophagy, or mitophagy, can sustain the archetypal properties of stem cells is incomplete. PTEN-induced putative kinase 1 (PINK1) plays a key role in the maintenance of mitochondrial morphology and function and in the selective degradation of damaged mitochondria by mitophagy. Here, using embryonic fibroblasts fromPINK1 gene-knockout (KO) mice, we evaluated whether mitophagy is a causal mechanism for the control of cell-fate plasticity and maintenance of pluripotency. Loss of PINK1-dependent mitophagy was sufficient to dramatically decrease the speed and efficiency of induced pluripotent stem cell (iPSC) reprogramming. Mitophagy-deficient iPSC colonies, which were characterized by a mixture of mature and immature mitochondria, seemed unstable, with a strong tendency to spontaneously differentiate and form heterogeneous populations of cells. Although mitophagy-deficient iPSC colonies normally expressed pluripotent markers, functional monitoring of cellular bioenergetics revealed an attenuated glycolysis in mitophagy-deficient iPSC cells. Targeted metabolomics showed a notable alteration in numerous glycolysis- and TCA-related metabolites in mitophagy-deficient iPSC cells, including a significant decrease in the intracellular levels of α-ketoglutarate -a key suppressor of the differentiation path in stem cells. Mitophagy-deficient iPSC colonies exhibited a notably reduced teratoma-initiating capacity, but fully retained their pluripotency and multi-germ layer differentiation capacity in vivo. PINK1-dependent mitophagy pathway is an important mitochondrial switch that determines the efficiency and quality of somatic reprogramming. Mitophagy-driven mitochondrial rejuvenation might contribute to the ability of iPSCs to suppress differentiation by directing bioenergetic transition and metabolome remodeling traits. These findings provide new insights into how mitophagy might influence the stem cell decisions to retain pluripotency or differentiate in tissue regeneration and aging, tumor growth, and regenerative medicine.
Áreas temáticas: Odontología Nutrição Medicina veterinaria Medicina iii Medicina ii Medicina i Interdisciplinar Geriatrics & gerontology Ciências biológicas ii Ciências biológicas i Cell biology Biotecnología
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: jorge.joven@urv.cat esther.rodriguez@urv.cat
Identificador del autor: 0000-0003-2749-4541
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.aging-us.com/article/100976/text
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Aging-Us. 8 (7): 1330-1352
Referencia de l'ítem segons les normes APA: Vazquez-Martin A, Van den Haute C, Cufí S, Corominas-Faja B, Cuyàs E, Lopez-Bonet E, Rodriguez-Gallego E, Fernández-Arroyo S, Joven J, Baekelandt V, M (2016). Mitophagy-driven mitochondrial rejuvenation regulates stem cell fate. Aging-Us, 8(7), 1330-1352. DOI: 10.18632/aging.100976
DOI del artículo: 10.18632/aging.100976
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2016
Tipo de publicación: Journal Publications
Repositori URV