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January 14, 2026Antioxidants and Redox Signaling0 citations

Activation of Mitophagy by Kinetin Mitigates Coal–Silica Mixed Dust-Induced Pulmonary Fibrosis via Modulating Macrophage Mitochondrial Function in Mice

MCMeiyu ChangNorth China University of Science and Technology QZQiang ZhouNorth China University of Science and Technology YGYi GuanNorth China University of Science and Technology

Key Points

This study explores the role of mitophagy in coal-silica mixed dust-induced pulmonary fibrosis and evaluates kinetin's therapeutic effects.
Examined the impact of coal-silica mixed dust exposure on mitochondrial function and inflammation in mice.
Investigated the role of PINK1/Parkin-mediated mitophagy in mitochondrial damage and inflammation.
Evaluated the therapeutic potential of kinetin in restoring mitochondrial integrity and function.
Coal-silica dust triggered reactive oxygen species accumulation and mitochondrial dysfunction.
Kinetin treatment restored PINK1/Parkin signaling and improved mitophagy, alleviating pulmonary fibrosis.
Kinetin's protective effects were diminished with PINK1 knockdown, confirming its crucial role in the therapy.

Abstract

Aims: Coal workers’ pneumoconiosis (CWP) is an occupational lung disease caused by the inhalation of coal dust. A key underlying pathogenic mechanism is driven by mitochondrial dysfunction and excessive reactive oxygen species (ROS), which trigger macrophage inflammation and cell death. Damaged mitochondria are selectively degraded via mitophagy, a process essential for maintaining mitochondrial homeostasis and promoting cell survival. However, the role of mitophagy dysregulation in dust-induced mitochondrial dysfunction and the underlying treatment with kinetin remain unclear. This study aimed to explore the role of PINK1/Parkin-mediated mitophagy in coal–silica mixed dust (CSD)-induced mitochondrial damage and to investigate the therapeutic potential of kinetin in targeting this pathway. Results: In this study, we compared the effects of CSD exposure and kinetin treatment on mitophagy, mitochondrial function, inflammation, and pulmonary fibrosis. We found that CSD exposure triggered ROS accumulation, mitochondrial membrane potential collapse, and impaired oxidative phosphorylation, leading to reduced adenosine triphosphate synthesis. Mechanistically, CSD suppressed PINK1/Parkin signaling and diminished LC3B mitochondrial recruitment, resulting in defective mitophagy. Notably, kinetin treatment and PINK1 overexpression restored PINK1/Parkin activation and LC3II-dependent mitophagy, alleviated mitochondrial dysfunction, and suppressed subsequent macrophage inflammation and pulmonary fibrosis. Genetic knockdown of PINK1 abolished the protective effects of kinetin, confirming a PINK1-dependent mechanism. Innovation: Our results revealed that kinetin is a PINK1-dependent mitophagy activator, positioning it as a promising therapeutic candidate for CWP by targeting mitochondrial integrity. Conclusion: Kinetin exerts its antifibrotic effects on CWP by promoting PINK1-mediated mitophagy, improving mitochondrial function, and alleviating macrophage inflammation. Antioxid. Redox Signal. 00, 000–000.

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