{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:10:31Z","timestamp":1789477831806,"version":"build-2803163510"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Diabetic retinopathy (DR) remains a leading cause of vision loss among working-age adults. Its pathogenesis is increasingly understood as the progressive dysregulation of the mitochondrial quality control (MQC) network, which encompasses mitochondrial dynamics, mitophagy, mitochondrial biogenesis, mitochondria-associated endoplasmic reticulum membranes (MAMs), and intercellular mitochondrial transfer. Under sustained hyperglycemia, this network shifts from compensatory imbalance to irreversible collapse, driving mitochondrial dysfunction, oxidative stress, inflammatory activation, and retinal neurovascular unit (NVU) injury, thus promoting progression from non-proliferative to proliferative DR. Because of their multitarget properties, natural products (NPs) can restore fusion-fission balance, modulate mitophagy in a stage-dependent manner, and promote mitochondrial biogenesis, thereby remodeling the MQC network. However, their clinical translation is constrained by low bioavailability, poor penetration of the blood-retinal barrier (BRB), and potential dose-dependent toxicity. Mitochondria-targeted nano-delivery systems, including liposomes, exosomes, and mitochondrial-derived vesicles, may improve retinal accumulation and mitochondrial targeting. Future studies should refine stage-specific mechanistic understanding, strengthen safety evaluation and structural optimization, and integrate single-cell omics with artificial intelligence to accelerate translation and enable early MQC-targeted intervention, with the potential to delay or even reverse the progression of DR. Critically, MQC-directed NP therapy should not be interpreted as uniformly pro-mitophagy, anti-fission, or pro-biogenesis; the therapeutic benefit depends on disease stage, cell type, autophagic flux integrity, target engagement, and retinal pharmacokinetic\/pharmacodynamic exposure.<\/jats:p>","DOI":"10.3389\/fphar.2026.1851846","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T06:11:57Z","timestamp":1782195117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Remodeling of the mitochondrial quality control network: natural products intervening in diabetic retinopathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Tingru","family":"Chen","sequence":"first","affiliation":[{"name":"Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruolan","family":"Wu","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Huang","sequence":"additional","affiliation":[{"name":"Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninghui","family":"Wan","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine Hospital of Meishan","place":["Meishan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1615103","DOI":"10.3389\/fendo.2025.1615103","article-title":"A key role of the PGC-1\u03b1\/ERR-\u03b1 pathway in regulation of angiogenic factors in proliferative diabetic retinopathy","volume":"16","author":"Abu El-Asrar","year":"2025","journal-title":"Front. 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