Mitochondrial Ca²⁺ homeostasis in ovarian function and oocyte competence: from molecular transporters to early embryonic development.

Authors

Xiaoqian Fu, Qianyi Huang, Huimei Wu, Lidan Liu

Published in

Frontiers in cell and developmental biology. Volume 14. Pages 1963467. Epub Sep 11, 2026.

Abstract

Mitochondrial Ca²⁺ homeostasis is a critical interface connecting ovarian cell signaling, energy metabolism, redox balance, and reproductive competence. Transient Ca²⁺ uptake into the mitochondrial matrix activates Ca²⁺-sensitive dehydrogenases, enhances reducing-equivalent generation, and supports oxidative phosphorylation. By contrast, sustained Ca²⁺ accumulation promotes reactive oxygen species production, membrane-potential collapse, mitochondrial permeability transition, and cell death. The identification of the mitochondrial calcium uniporter together with its regulators MICU1, MICU2, and EMRE, has established a molecular framework for mitochondrial Ca²⁺ influx. NCLX and its interacting protein TMEM65 contribute to Ca²⁺ efflux and determine recovery after individual Ca²⁺ transients. In ovarian cells and oocytes, endoplasmic reticulum (endoplasmic reticulum)-mitochondria contact sites, including the IP₃R1-GRP75-VDAC1 axis, couple cytosolic Ca²⁺ signals to mitochondrial metabolism. Evidence from mouse, porcine, avian, zebrafish, Xenopus, and sea-urchin models implicates mitochondrial Ca²⁺ in follicular-cell survival, oocyte meiotic maturation, fertilization-associated Ca²⁺ oscillations, the oocyte-to-embryo transition, and early embryonic development. Obesity, aging, cryopreservation, heavy metals, environmental chemicals, and oxidative stress can disturb this system. However, mitochondrial Ca²⁺ dysregulation is not always readily separable from broader mitochondrial or ER dysfunction. Major limitations of the current literature include reliance on non-selective pharmacological agents, incomplete calibration of organelle-targeted indicators, insufficient temporal resolution, interspecies differences, and limited direct evidence from human oocytes. Future studies should integrate cell-type-specific genetic perturbation, quantitative multi-organelle Ca²⁺ imaging, mitochondrial bioenergetics, and long-term developmental assessment. Mitochondrial Ca²⁺ is a promising mechanistic node and candidate biomarker, but it is not yet a validated clinical target in reproductive medicine.

PMID:
42798439
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.