Molecular medicine reportsJun 11, 2026

Melatonin reduces mitochondrial damage by controlling energy regulators in egg cells under PCOS-like conditions

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 12, 2026

Abstract

Granulosa cells from patients with polycystic ovary syndrome (PCOS) showed mitochondrial dysfunction.

Decreased expression of SIRT3 was observed in granulosa cells treated with dihydrotestosterone (DHT).
DHT treatment led to dysregulated mitochondrial dynamics and hyperactivation of the cellular process that removes damaged mitochondria.
Melatonin (MT) treatment and SIRT3 overexpression restored mitochondrial membrane potential and rebalanced mitochondrial dynamics in DHT-treated cells.
Reduced levels of MT were found in the follicular fluid of patients with PCOS.
The protective effects of MT on mitochondrial dynamics and autophagy proteins were negated when SIRT3 was inhibited.

Simplified

The present study investigated the role of melatonin (MT) in regulating mitochondrial function via sirtuin 3 (SIRT3) in granulosa cells (GCs) from patients with polycystic ovary syndrome (PCOS), with a focus on mitochondrial protection. Notably, GCs isolated from patients with PCOS exhibited mitochondrial dysfunction. Using anPCOS model established by treating KGN cells with dihydrotestosterone (DHT), decreased SIRT3 expression, dysregulated mitochondrial dynamics and hyperactivation of mitophagy were observed. Both SIRT3 overexpression and MT treatment restored the mitochondrial membrane potential, rebalanced mitochondrial dynamics and suppressed excessive autophagy in DHT‑treated cells. Additionally, MT levels were shown to be reduced in the follicular fluid of patients with PCOS. Notably, the protective effects of MT on proteins associated with both mitochondrial dynamics and autophagy were abolished upon SIRT3 inhibition. In conclusion, mitochondrial dysfunction and aberrant mitophagy in GCs may serve a role in the pathogenesis of PCOS. MT appears to ameliorate these defects by modulating mitochondrial dynamics and function in a SIRT3‑dependent manner. Moreover, the current study identified SIRT3 as a key molecular target of MT in PCOS. in vitro

Funding

Competing interests

The authors declare that they have no competing interests.

PubMed

Melatonin reduces mitochondrial damage by controlling energy regulators in egg cells under PCOS-like conditions

Abstract

Funding

Competing interests

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