Photobiomodulation mediates endoplasmic reticulum-mitochondria contact and ameliorates lipotoxicity in MASLD via Mfn2 upregulation

IF 3.7 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of photochemistry and photobiology. B, Biology Pub Date : 2025-07-02 DOI:10.1016/j.jphotobiol.2025.113209

Zhixuan Jiang , Shan Wu , Shengzhe Zhou , Hongjie Zheng , Yubing Bai , Yiqiu Zhang , Min Yao

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引用次数: 0

Abstract

The disruption of mitochondria associated membranes (MAMs) is involved in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) by modulating endoplasmic reticulum stress (ERS) and mitochondrial malfunction induced by lipotoxicity. Photobiomodulation (PBM), as a non-invasive physical therapy, has been demonstrated to improve cellular metabolism in various diseases. Here we found that PBM with 650 nm ameliorated lipid accumulation and liver injury in high-fat-diet-fed mice. Moreover, MAMs integrity was restored in liver tissues of MASLD after PBM. Correspondingly, PBM enhanced mitochondria-ER colocalization and improved mitochondrial homeostasis in fatty-acid-treated HepG2 cells. Mechanically, Mfn2 expression was selectively elevated by PBM, accompanied by downregulation of PERK, p-PERK, and CHOP. The beneficial effects of PBM were diminished by Mfn2 knockdown, while PERK activity regulated oxidative stress without altering MAMs formation. Thus, PBM relieves lipotoxicity in MASLD by enhancing MAMs integrity via the Mfn2/PERK/CHOP pathway. Our findings may provide evidence for noninvasive physical light therapeutics for lifestyle-related metabolic diseases.

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光生物调节介导内质网-线粒体接触，并通过Mfn2上调改善MASLD的脂肪毒性

线粒体相关膜（MAMs）的破坏通过调节内质网应激（ERS）和脂肪毒性诱导的线粒体功能障碍参与代谢功能障碍相关脂肪变性肝病（MASLD）的发病机制。光生物调节（PBM）作为一种非侵入性的物理疗法，已被证明可以改善多种疾病的细胞代谢。本研究发现，650 nm的PBM改善了高脂饮食小鼠的脂质积累和肝损伤。此外，PBM后MASLD肝组织中MAMs的完整性得到恢复。相应地，PBM在脂肪酸处理的HepG2细胞中增强线粒体-内质网共定位并改善线粒体稳态。机械上，PBM选择性上调Mfn2表达，同时下调PERK、p-PERK和CHOP。Mfn2敲低降低了PBM的有益作用，而PERK活性在不改变MAMs形成的情况下调节氧化应激。因此，PBM通过Mfn2/PERK/CHOP途径增强MAMs的完整性，从而减轻MASLD中的脂肪毒性。我们的发现可能为无创物理光治疗与生活方式相关的代谢疾病提供证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of photochemistry and photobiology. B, Biology 生物-生化与分子生物学

CiteScore

12.10

自引率

1.90%

发文量

161

审稿时长

37 days

期刊介绍： The Journal of Photochemistry and Photobiology B: Biology provides a forum for the publication of papers relating to the various aspects of photobiology, as well as a means for communication in this multidisciplinary field. The scope includes: - Bioluminescence - Chronobiology - DNA repair - Environmental photobiology - Nanotechnology in photobiology - Photocarcinogenesis - Photochemistry of biomolecules - Photodynamic therapy - Photomedicine - Photomorphogenesis - Photomovement - Photoreception - Photosensitization - Photosynthesis - Phototechnology - Spectroscopy of biological systems - UV and visible radiation effects and vision.