What does this research mean for the field?

A positive feedback loop between Drp1-mediated mitochondrial fragmentation and succinate accumulation via succinate dehydrogenase (SDH) suppression promotes hepatocellular carcinoma growth and metastasis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine whether excessive mitochondrial fragmentation suppresses succinate dehydrogenase expression and drives succinate accumulation and secretion in hepatocellular carcinoma.

August 28, 2026Journal of Biomedical ScienceOpen Access

Rebalancing mitochondrial dynamics restores succinate dehydrogenase activity and reduces succinate release in hepatocellular carcinoma

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Authors

JWJing-Yiing WuNational Health Research Institutes TCTzu‐Ching ChangCalifornia Institute of Technology MCMei-Jen ChenNational Health Research Institutes

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Implication

Translational study reveals that inhibiting mitochondrial fragmentation restores succinate dehydrogenase in hepatocellular carcinoma, indicating a therapeutic approach to curb tumor progression.

Key Points

To determine whether excessive mitochondrial fragmentation suppresses succinate dehydrogenase expression and drives succinate accumulation and secretion in hepatocellular carcinoma.
Evaluated human hepatocellular carcinoma (HCC) cell lines (Huh7), murine xenograft models, patient tumor tissue specimens, and patient serum samples.
Modulated mitochondrial fission using genetic suppression and pharmacological inhibition of dynamin-related protein 1 (Drp1) via Mdivi-1, alongside SDHB overexpression and siRNA-mediated silencing.
Human HCC tissues and serum showed reduced SDHB mRNA and elevated succinate levels, with higher SDHB expression correlating with improved overall and relapse-free survival.
Genetic or pharmacological inhibition of Drp1 restored SDHB expression, reduced succinate levels, and decreased tumor growth and lung metastasis in xenograft models.
Exogenous succinate enhanced Drp1-mediated mitochondrial fragmentation whereas SDHB overexpression suppressed Drp1 activation, demonstrating a positive feedback regulatory loop.

Cite This Study

Wu et al. (2026) studied this question.

synapsesocial.com/papers/6a91467bd15324a1df3aa27e https://doi.org/10.1186/s12929-026-01289-0

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Implication

Translational study reveals that inhibiting mitochondrial fragmentation restores succinate dehydrogenase in hepatocellular carcinoma, indicating a therapeutic approach to curb tumor progression.

Rebalancing mitochondrial dynamics restores succinate dehydrogenase activity and reduces succinate release in hepatocellular carcinoma

Discussion

Member takes

Implication

Key Points

Cite This Study

Rebalancing mitochondrial dynamics restores succinate dehydrogenase activity and reduces succinate release in hepatocellular carcinoma

Discussion

Member takes

Implication

Key Points

Cite This Study

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