Phosphoglycerate mutase family member 5 maintains oocyte quality via mitochondrial dynamic rearrangement during aging

Abstract

Decline in ovarian reserve with aging is associated with reduced fertility and the development of metabolic abnormalities. Once mitochondrial homeostasis is imbalanced, it may lead to poor reproductive cell quality and aging. However, Phosphoglycerate translocase 5 (PGAM5), located in the mitochondrial membrane, is associated with necroptosis, apoptosis, and mitophagy, although the underlying mechanisms associated with ovarian aging remain unknown. Therefore, we attempted to uncover whether the high phosphoglycerate mutant enzyme family member 5 (PGAM5) expression is associated with female infertility in cumulus cells, and aims to find out the underlying mechanism of action of PGAM5. We found that PGAM5 is highly expressed and positively associated with aging, and has the potential to help maintain and regulate mitochondrial dynamics and metabolic reprogramming in aging granulosa cells, ovaries of aged female mice, and elderly patients. PGAM5 undergoes activation in the aging group and translocated to the outer membrane of mitochondria, co‐regulating DRP1; thereby increasing mitochondrial fission. A significant reduction in the quality of mitochondria in the aging group, a serious imbalance, and a significant reduction in energy, causing metabolism shift toward glycolysis, were also reported. Since PGAM5 is eliminated, the mitochondrial function and metabolism of aging cells are partially reversed. A total of 70 patients undergoing in vitro fertilization (IVF) treatment were recruited in this clinical study. The high expression of PGAM5 in the cumulus cells is negatively correlated with the pregnancy rate of infertile patients. Hence, PGAM5 has immense potential to be used as a diagnostic marker.

Alterations of Lipid-Mediated Mitophagy Result in Aging-Dependent Sensorimotor Defects

“…Mitochondrial ribosomes and ribosomal proteins are associated with the inner mitochondrial membranes and mitochondrial matrix in metabolically healthy mitochondria. However, during Drp1/Pink1/Parkinmediated fission, membrane reorganization occurs between inner and outer mitochondrial membranes [27][28][29][30] . We hypothesize that mitochondrial membrane rearrangements are critical in recruiting the p17/PERMIT-CerS1 complex to mitochondria.…”

Oviductal Extracellular Vesicles Enhance Porcine In Vitro Embryo Development by Modulating the Embryonic Transcriptome

“…The overexpression of PGAM5 has been shown to trigger mitophagic cell death [ 95 ]. Besides, an increased PGAM5 expression has been related to aging, with higher PGAM5 expression in in vitro human aged cumulus cells, in murine aged oocytes, and in the cumulus cells of older women compared to their young counterparts [ 96 ]. This has been associated with a higher mitochondrial fragmentation that leads to apoptosis, causing imbalance of mitochondria dynamics and affecting the energy capacity of mitochondria in cells.…”

“…This has been associated with a higher mitochondrial fragmentation that leads to apoptosis, causing imbalance of mitochondria dynamics and affecting the energy capacity of mitochondria in cells. Thus, reducing PGAM5 expression has been suggested as a way to ensure proper oocyte and mitochondrial activity, to avoid oxidative damage and energy deficiency, and thus, slow down the aging process [ 96 ]. On the other hand, miR-21-5p has been shown to directly suppress mitophagy and mitochondrial damage by targeting PGAM5 [ 97 ].…”

Plasma-derived phosphoglycerate mutase 5 as a biomarker for Parkinson’s disease

“…A current study on the connection of PGAM5 and reproductive cell showed that PGAM5 was highly expressed and positively associated with aging; a total of 70 patients were recruited in this clinical study. As the researcher described, when PGAM5 is eliminated, the mitochondrial function and metabolism of aging cells are partially reversed ( Li et al, 2022 ). In our study, plasma PGAM5 levels were higher among elderly participants (>60 years) in PD group compared with HC group, this result also indicates that PGAM5 may have some association with aging.…”