ArticleJCI insight2022
Hepatic Fis1 regulates mitochondrial integrated stress response and improves metabolic homeostasis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation.Cell reports · 2026Article
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- From symbiosis to immunity: the evolutionary revival of mitochondrial defense programs in inflammatory diseases.Cell communication and signaling : CCS · 2026Review
- Mitochondrial Calcium Signaling in Hepatocyte Health and Disease.Cold Spring Harbor perspectives in biology · 2026Review
- The role of FIS1 and its post-translational modifications in diseases and health damage caused by environmental pollution.Cell biology and toxicology · 2025Review
- Mitochondrial dysfunction in mesenchymal stem cells impairs osteogenesis in radiation-induced bone injury via CaCell death & disease · 2025Article
- Hepatocyte FAM210A deficiency disrupts mitochondrial function and triggers juvenile steatosis with compensatory repair in adulthood.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial FIS1 As a Novel Drug Target for the Treatment of Erectile Dysfunction: A Multi-Omic and Epigenomic Association Study.The world journal of men's health · 2025Article
- Mitochondrial dynamics and quality control regulate proteostasis in neuronal ischemia-reperfusion.Autophagy · 2025Article
- Preadipocyte IL-13/IL-13Rα1 signaling regulates beige adipogenesis through modulation of PPARγ activity.The Journal of clinical investigation · 2025Article
- Therapeutic potential of monomethyl fumarate and aluminum ion combination in alleviating inflammation and oxidative stress in psoriasis.Redox biology · 2025Article
- Article
- High-Fat Diets Fed during Pregnancy Cause Changes to Pancreatic Tissue DNA Methylation and Protein Expression in the Offspring: A Multi-Omics Approach.International journal of molecular sciences · 2024Article
- Low Protein Programming Causes Increased Mitochondrial Fusion and Decreased Oxygen Consumption in the Hepatocytes of Female Rats.Nutrients · 2023Article
- ATF5 Attenuates the Secretion of Pro-Inflammatory Cytokines in Activated Microglia.International journal of molecular sciences · 2023Article
- PFOS Impairs Mitochondrial Biogenesis and Dynamics and Reduces Oxygen Consumption in Human Trophoblasts.Journal of environmental science and public health · 2023Article
- Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT.Scientific reports · 2022Article
- T-cell Metabolism as Interpreted in Obesity-associated Inflammation.Endocrinology · 2022Article
- Advancements in Activating Transcription Factor 5 Function in Regulating Cell Stress and Survival.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Mitophagy and mitochondrial integrated stress response (ISR) are 2 primary protective mechanisms to maintain functional mitochondria. Whether these 2 processes are coordinately regulated remains unclear. Here we show that mitochondrial fission 1 protein (Fis1), which is required for completion of mitophagy, serves as a signaling hub linking mitophagy and ISR. In mouse hepatocytes, high fat diet (HFD) feeding induces unresolved oxidative stress, defective mitophagy and enhanced type I interferon (IFN-I) response implicated in promoting metabolic inflammation. Adenoviral-mediated acute hepatic Fis1 overexpression is sufficient to reduce oxidative damage and improve glucose homeostasis in HFD-fed mice. RNA-Seq analysis reveals that Fis1 triggers a retrograde mitochondria-to-nucleus communication upregulating ISR genes encoding anti-oxidant defense, redox homeostasis, and proteostasis pathways. Fis1-mediated ISR also suppresses expression of IFN-I-stimulated genes through activating transcription factor 5 (Atf5), which inhibits the transactivation activity of interferon regulatory factor 3 (Irf3) known to control IFN-I production. Metabolite analysis demonstrates that Fis1 activation leads to accumulation of fumarate, a TCA cycle intermediate capable of increasing Atf5 activity. Consequently, hepatic Atf5 overexpression or monomethyl fumarate (MMF) treatment improves glucose homeostasis in HFD-fed mice. Collectively, these results support the potential use of small molecules targeting the Fis1-Atf5 axis, such as MMF, to treat metabolic diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.