---
title: "PINK1-Parkin–Mediated Mitophagy in Sepsis: Mechanisms, Controversies, and Therapeutic Targets"
id: "pubmed-42667342"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42667342"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42667342/"
doi: "10.1007/s11033-026-12690-1"
published_at: "2026-08-29T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PINK1-Parkin–Mediated Mitophagy in Sepsis: Mechanisms, Controversies, and Therapeutic Targets
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42667342
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42667342/)
- **DOI:** [10.1007/s11033-026-12690-1](https://doi.org/10.1007%2Fs11033-026-12690-1)
- **Published At:** 2026-08-29T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The review examines the role of the **PINK1-Parkin pathway** in canonical **mitophagy** and its involvement in sepsis and sepsis-induced multiorgan dysfunction. - Mitophagy interacts with multiple pathogenic axes in sepsis, including **oxidative stress**, the **cGAS-STING** innate immune pathway, **NF-κB** signaling, and **inflammasome** activation. - The precise orchestration of mitophagy during mitochondrial damage in sepsis remains incompletely defined, and the pathway's net effect in sepsis is controversial. - The authors propose four key mechanistic pathways that link mitochondrial quality control to sepsis pathogenesis and inflammation. - The review identifies candidate therapeutic approaches that modulate the PINK1-Parkin pathway by mechanism: **PINK1 activators**, **Parkin recruiters**, **deubiquitinase inhibitors**, and **upstream pathway modulators**. - Regulating mitophagy via the PINK1-Parkin axis may protect against multiple organ injuries reported in sepsis models and clinical settings, including **septic encephalopathy**, **cardiac dysfunction**, **acute lung injury**, and **acute kidney injury**. - The review is a synthesis of existing literature; detailed mechanistic steps, quantitative outcomes, and specific agent names or clinical results were not reported in the abstract and must be sought in the full article or primary studies. - Keywords highlighted by the work include Mitophagy, Multiorgan dysfunction, PINK1-Parkin pathway, and Sepsis.
## Clinical Analysis & Structured Key Points
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[Xiaoyan Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+X&cauthor_id=42667342)[#](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-affiliation-1 "Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China."), [Ke Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+K&cauthor_id=42667342)[#](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-affiliation-2 "College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China."), [Junshuai Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+J&cauthor_id=42667342)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-affiliation-3 "Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, 1095 JieFang Avenue, Hubei, Wuhan, China. wangjunshuai@tjh.tjmu.edu.cn.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-affiliation-4 "Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, China. wangjunshuai@tjh.tjmu.edu.cn."), [Yang He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Y&cauthor_id=42667342)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#full-view-affiliation-5 "Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China. wuhanheyang908@163.com.") Affiliations Expand ### Affiliations * 1 Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China. * 2 College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China. * 3 Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, 1095 JieFang Avenue, Hubei, Wuhan, China. wangjunshuai@tjh.tjmu.edu.cn. * 4 Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, China. wangjunshuai@tjh.tjmu.edu.cn. * 5 Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China. wuhanheyang908@163.com. # Contributed equally. * PMID: **42667342** * DOI: [ 10.1007/s11033-026-12690-1 ](https://doi.org/10.1007/s11033-026-12690-1) Item in Clipboard Review # PINK1-Parkin pathway-mediated mitophagy in sepsis: friend or foe? Xiaoyan Wu et al. Mol Biol Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Mol Biol Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mol+Biol+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Mol+Biol+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) . 2026 Aug 29;53(1):1488. doi: 10.1007/s11033-026-12690-1. ### Authors [Xiaoyan Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+X&cauthor_id=42667342)[#](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-affiliation-1 "Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China."), [Ke Ma](https://pubmed.ncbi.nlm.nih.gov/?term=Ma+K&cauthor_id=42667342)[#](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-affiliation-2 "College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China."), [Junshuai Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+J&cauthor_id=42667342)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-affiliation-3 "Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, 1095 JieFang Avenue, Hubei, Wuhan, China. wangjunshuai@tjh.tjmu.edu.cn.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-affiliation-4 "Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, China. wangjunshuai@tjh.tjmu.edu.cn."), [Yang He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Y&cauthor_id=42667342)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42667342/#short-view-affiliation-5 "Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China. wuhanheyang908@163.com.") ### Affiliations * 1 Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China. * 2 College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China. * 3 Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, 1095 JieFang Avenue, Hubei, Wuhan, China. wangjunshuai@tjh.tjmu.edu.cn. * 4 Department of Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, Hubei, China. wangjunshuai@tjh.tjmu.edu.cn. * 5 Department of Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, Hubei, China. wuhanheyang908@163.com. # Contributed equally. * PMID: **42667342** * DOI: [ 10.1007/s11033-026-12690-1 ](https://doi.org/10.1007/s11033-026-12690-1) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract The PINK1-Parkin pathway is well-known for its role in canonical mitophagy, which is involved in various mitophagy-related biological and pathological processes, including pathogen infection, inflammasome activation, oxidative stress, inflammatory response, and even sepsis-induced multiorgan dysfunction. However, the precise mechanisms by which mitophagy is orchestrated during mitochondrial damage and its role in sepsis-induced multiple organ dysfunction are not yet fully elucidated, and there is even controversy. This review proposes four key mechanistic pathways-oxidative stress, the cGAS-STING axis, NF-κB signaling, and inflammasome activation-that interact with mitophagy and contribute to sepsis pathogenesis. Another objective of the work is to explore potential candidate agents that regulate the PINK1-Parkin pathway in mitophagy, by therapeutic mechanism (e.g. PINK1 activators, Parkin recruiters, deubiquitinase inhibitors and upstream pathway modulators). The therapeutic benefits can be achieved by regulating mitophagy, which has promising protective effects against multi-organ injuries, including septic encephalopathy, cardiac dysfunction, acute lung injury, and acute kidney injury. **Keywords:** Mitophagy; Multiorgan dysfunction; PINK1-Parkin pathway; Sepsis. © 2026. The Author(s), under exclusive licence to Springer Nature B.V. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. ## References 1. 1. Singer M, Deutschman CS, Seymour CW et al (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315(8):801–810. - [DOI](https://doi.org/10.1001/jama.2016.0287) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26903338/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4968574/) 2. 1. Sliter DA, Martinez J, Hao L et al (2018) Parkin and PINK1 mitigate STING-induced inflammation. Nature 561(7722):258–262. - [DOI](https://doi.org/10.1038/s41586-018-0448-9) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/30135585/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/7362342/) 3. 1. Fu C, Weng S, Liu D et al (2025) Review on the Role of Mitochondrial Dysfunction in Septic Encephalopathy. Cell Biochem Biophys 83(1):135–145. - [DOI](https://doi.org/10.1007/s12013-024-01493-5) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/39212823/) 4. 1. Bader V, Winklhofer KF (2020) PINK1 and Parkin: team players in stress-induced mitophagy. Biol Chem 401(6–7):891–899. - [DOI](https://doi.org/10.1515/hsz-2020-0135) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32297878/) 5. 1. Li J, Yang D, Li Z et al (2023) PINK1/Parkin-mediated mitophagy in neurodegenerative diseases. Ageing Res Rev 84:101817. - [DOI](https://doi.org/10.1016/j.arr.2022.101817) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/36503124/) Show all 100 references ## Publication types * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Inflammasomes / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Inflammasomes%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Inflammasomes) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Mitochondria / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mitochondria%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mitochondria) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Mitophagy* / physiology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mitophagy%2Fphysiology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Mitophagy) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * NF-kappa B / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22NF-kappa+B%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=NF-kappa+B) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Oxidative Stress Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Oxidative+Stress%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Oxidative+Stress) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * PTEN-Induced Putative Kinase Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22PTEN-Induced+Putative+Kinase%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=PTEN-Induced+Putative+Kinase) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Protein Kinases* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Protein+Kinases%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Protein+Kinases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Protein Kinases* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Protein+Kinases%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Protein+Kinases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Sepsis* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sepsis%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Sepsis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Sepsis* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sepsis%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Sepsis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42667342/) * Signal Transduction Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Signal+Transduction%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeS
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