Polycystin-1 regulates cardiomyocyte mitophagy

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dc.contributor.authorRamirez-Sagredo, Andrea
dc.contributor.authorQuiroga, Clara
dc.contributor.authorGarrido-Moreno, Valeria
dc.contributor.authorLopez-Crisosto, Camila
dc.contributor.authorLeiva-Navarrete, Sebastian
dc.contributor.authorNorambuena-Soto, Ignacio
dc.contributor.authorOrtiz-Quintero, Jafet
dc.contributor.authorDiaz-Vesga, Magda C.
dc.contributor.authorPerez, William
dc.contributor.authorHendrickson, Troy
dc.contributor.authorParra, Valentina
dc.contributor.authorPedrozo, Zully
dc.contributor.authorAltamirano, Francisco
dc.contributor.authorChiong, Mario
dc.contributor.authorLavandero, Sergio
dc.date.accessioned2025-01-20T22:12:00Z
dc.date.available2025-01-20T22:12:00Z
dc.date.issued2021
dc.description.abstractPolycystin-1 (PC1) is a transmembrane protein found in different cell types, including cardiomyocytes. Alterations in PC1 expression have been linked to mitochondrial damage in renal tubule cells and in patients with autosomal dominant polycystic kidney disease. However, to date, the regulatory role of PC1 in cardiomyocyte mitochondria is not well understood. The analysis of mitochondrial morphology from cardiomyocytes of heterozygous PC1 mice (PDK1(+/-)) using transmission electron microscopy showed that cardiomyocyte mitochondria were smaller with increased mitochondria density and circularity. These parameters were consistent with mitochondrial fission. We knocked-down PC1 in cultured rat cardiomyocytes and human-induced pluripotent stem cells (iPSC)-derived cardiomyocytes to evaluate mitochondrial function and morphology. The results showed that downregulation of PC1 expression results in reduced protein levels of sub-units of the OXPHOS complexes and less functional mitochondria (reduction of mitochondrial membrane potential, mitochondrial respiration, and ATP production). This mitochondrial dysfunction activates the elimination of defective mitochondria by mitophagy, assessed by an increase of autophagosome adapter protein LC3B and the recruitment of the Parkin protein to the mitochondria. siRNA-mediated PC1 knockdown leads to a loss of the connectivity of the mitochondrial network and a greater number of mitochondria per cell, but of smaller sizes, which characterizes mitochondrial fission. PC1 silencing also deregulates the AKT-FoxO1 signaling pathway, which is involved in the regulation of mitochondrial metabolism, mitochondrial morphology, and processes that are part of cell quality control, such as mitophagy. Together, these data provide new insights about the controls that PC1 exerts on mitochondrial morphology and function in cultured cardiomyocytes dependent on the AKT-FoxO1 signaling pathway.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.202002598R
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.202002598R
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94423
dc.identifier.wosidWOS:000678975300004
dc.issue.numero8
dc.language.isoen
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectcardiomyocyte
dc.subjectFoxO1
dc.subjectmitochondrial dynamics
dc.subjectmitochondrial metabolism
dc.subjectmitophagy
dc.subjectpolycystin-1
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePolycystin-1 regulates cardiomyocyte mitophagy
dc.typeartículo
dc.volumen35
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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