ArticleAutophagy2016
Increased mitochondrial fission promotes autophagy and hepatocellular carcinoma cell survival through the ROS-modulated coordinated regulation of the NFKB and TP53 pathways.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers.
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238 citing papers in PubMed, 386 citations in OpenAlex.
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- Electron transport chain complex I and mitochondrial fusion regulate ROS for differentiation in Drosophila neural stem cells.Stem cell reports · 2026Article
- ZG16 represses tumor progression and M2 polarization of tumor-associated macrophages in hepatocellular carcinoma by promoting ubiquitination and degradation of SNX9 via binding to ITCH.Hepatology international · 2026Article
- Induction of mitochondrial fission and mtDNA leakage via the Smad3/Drp1 axis by PEDV infection activates the TLR9/NF-κB/IL-1β inflammatory pathway.Virologica Sinica · 2026Article
- Imbalances of mitochondrial dynamics in solid tumors.Oncogenesis · 2026Review
- Time-Dependent Effects of Cisplatin on Autophagy Gene Expression in Bladder Cancer Cells.Biomedicines · 2026Article
- Association of Autophagy-Related Gene Expression Profiles with Survival in Diffuse Astrocytic Tumors.Cancers · 2026Article
- Mitochondrial dynamics and cancer: mechanisms and targeted therapy.Cell biology and toxicology · 2026Review
- HIF-1α suppresses SNPH expression to facilitate liver metastasis of colorectal cancer through regulating mitochondrial dynamics and filopodia formation.Cell death & disease · 2026Article
- Mitochondrial Calcium Signaling in Hepatocyte Health and Disease.Cold Spring Harbor perspectives in biology · 2026Review
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- Proteomic analysis of mitochondria-ER contacts reveals key proteins involved in metabolic regulation in hepatocytes.Cell communication and signaling : CCS · 2026Article
- Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects.Molecular cancer · 2026Review
- MTP18 as a prognostic biomarker and therapeutic target in lung adenocarcinoma.Respiratory research · 2026Article
- Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.Scientific reports · 2026Article
- Increasing autophagy activity suppressesAmerican journal of cancer research · 2026Article
- Mitochondria-related genes or proteins affect the progression of hepatocellular carcinoma: roles, mechanisms and potential treatments.American journal of cancer research · 2026Review
- Transcriptome-based profiling of programmed cell death signatures identifies two osteoarthritis subtypes and the hub gene DNM1L.Frontiers in immunology · 2026Article
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
178 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial morphology is dynamically remodeled by fusion and fission in cells, and dysregulation of this process is closely implicated in tumorigenesis. However, the mechanism by which mitochondrial dynamics influence cancer cell survival is considerably less clear, especially in hepatocellular carcinoma (HCC). In this study, we systematically investigated the alteration of mitochondrial dynamics and its functional role in the regulation of autophagy and HCC cell survival. Furthermore, the underlying molecular mechanisms and therapeutic application were explored in depth. Mitochondrial fission was frequently upregulated in HCC tissues mainly due to an elevated expression ratio of DNM1L to MFN1, which significantly contributed to poor prognosis of HCC patients. Increased mitochondrial fission by forced expression of DNM1L or knockdown of MFN1 promoted the survival of HCC cells both in vitro and in vivo mainly by facilitating autophagy and inhibiting mitochondria-dependent apoptosis. We further demonstrated that the survival-promoting role of increased mitochondrial fission was mediated via elevated ROS production and subsequent activation of AKT, which facilitated MDM2-mediated TP53 degradation, and NFKBIA- and IKK-mediated transcriptional activity of NFKB in HCC cells. Also, a crosstalk between TP53 and NFKB pathways was involved in the regulation of mitochondrial fission-mediated cell survival. Moreover, treatment with mitochondrial division inhibitor-1 significantly suppressed tumor growth in an in vivo xenograft nude mice model. Our findings demonstrate that increased mitochondrial fission plays a critical role in regulation of HCC cell survival, which provides a strong evidence for this process as drug target in HCC treatment.
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