Last update 01 Nov 2024

FIS1

Last update 01 Nov 2024

Basic Info

Synonyms

CGI-135, FIS1, FIS1 homolog

+ [7]

Introduction

Involved in the fragmentation of the mitochondrial network and its perinuclear clustering (PubMed:12783892, PubMed:12861026, PubMed:14996942, PubMed:23283981). Plays a minor role in the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface and mitochondrial fission (PubMed:12861026, PubMed:16118244, PubMed:23283981, PubMed:23530241, PubMed:24196833). May not be essential for the assembly of functional fission complexes and the subsequent membrane scission event (PubMed:23530241, PubMed:24196833). Also mediates peroxisomal fission (PubMed:16107562). May act when the products of fission are directed toward mitochondrial homeostasis, mitophagy, or apoptosis (PubMed:24196833). Can induce cytochrome c release from the mitochondrion to the cytosol, ultimately leading to apoptosis (PubMed:12783892).

Drugs associated with FIS1

P-110 (Stanford University)

Target

DNM1L x FIS1

Mechanism

DNM1L inhibitors [+1]

Active Org.

Case Western Reserve University School of Medicine

Originator Org.

Stanford University

Active Indication

Parkinson Disease

Inactive Indication

Alzheimer Disease [+1]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with FIS1

100 Translational Medicine associated with FIS1

0 Patents (Medical) associated with FIS1

907

Literatures (Medical) associated with FIS1

01 Jan 2025·Journal of Ethnopharmacology

Study on the role of Dihuang Yinzi in regulating the AMPK/SIRT1/PGC-1α pathway to promote mitochondrial biogenesis and improve Alzheimer's disease

Article

Author: He, Wenbin ; Han, Cheng ; Li, Qinqing ; Zhang, Zheng ; Hou, Jiangqi ; Zhang, Junlong ; Du, Yuzhong ; Zhu, Yousong ; Zhao, Qiong ; Qin, Yali ; Zhu, Chao

ETHNOPHARMACOLOGICAL RELEVANCEDihuang Yinzi (DHYZ) is a classic prescription in traditional Chinese medicine. Its therapeutic effect on Alzheimer's disease (AD) has been widely validated. However, the underlying molecular mechanisms of DHYZ in AD treatment remain unclear and require further research.AIM OF THE STUDYElucidating DHYZ's promotion of mitochondrial biogenesis through the AMPK/SIRT1/PGC-1α pathway improves neuronal loss, mitochondrial damage, and memory deficits in AD.MATERIALS AND METHODSAdministering DHYZ by gavage to SAMP8 mice, after completing behavioral tests, the effects of DHYZ on hippocampal neuron loss and mitochondrial structural damage in AD model mice were assessed using Nissl staining and transmission electron microscopy. Western blot was used to detect the expression of mitochondrial biogenesis-related proteins PGC-1α, CREB, mitochondrial fusion protein MFN2, and mitochondrial fission proteins DRP1 and FIS1. At the same time, immunofluorescence (IF) was employed to measure the relative fluorescence intensity of mitochondrial fusion protein MFN1. After determining the optimal dose of DYHZ for treating AD, we conducted mechanistic studies. By intraperitoneally injecting SAMP8 mice with the AMPK inhibitor (Compound C) to inhibit AMPK protein expression and subsequently treating them with DHYZ, the impact of DHYZ on hippocampal neurons in AD model mice was evaluated using Nissl and hematoxylin-eosin staining. Western blot was used to detect the protein expression of AMPK, p-AMPK, SIRT1, PGC-1α, NRF1, and TFAM. In contrast, IF was used to measure the relative fluorescence intensity of PGC-1α, NRF1, and TFAM proteins in the hippocampal CA1 region.RESULTSDHYZ significantly improved AD model mice's cognitive impairment and memory deficits and mitigated hippocampal neuron loss and degeneration. Additionally, it ameliorated mitochondrial morphological structures. DHYZ upregulated the protein expression of mitochondrial biogenesis-related proteins PGC-1α, CREB, and mitochondrial fusion proteins MFN1 and MFN2 while inhibiting the expression of mitochondrial fission proteins DRP1 and FIS1. Further studies revealed that DHYZ could upregulate the expression of the AMPK/SIRT1/PGC-1α pathway proteins and their downstream proteins NRF1 and TFAM.CONCLUSIONDHYZ promotes mitochondrial biogenesis by activating the AMPK/SIRT1/PGC-1α signaling pathway, thereby improving memory deficits, neuronal loss, and mitochondrial dysfunction in AD.

31 Dec 2024·Journal of the International Society of Sports Nutrition

Oral post-exercise garlic extract supplementation enhances glycogen replenishment but does not up-regulate mitochondria biogenesis mRNA expression in human-exercised skeletal muscle

Article

Author: Tsai, Tsen-Wei ; Bernard, Jeffrey R ; Chang, Chia-Chen ; Tsao, Jung-Piao ; Liao, Su-Fen ; Cheng, I-Shiung

PURPOSEGarlic extract (GA) is purported to enhance antioxidant and anti-inflammatory activity and glucose regulation in humans. The present study investigated the effects of post-exercise GA supplementation on GLUT4 expression, glycogen replenishment, and the transcript factors involved with mitochondrial biosynthesis in exercised human skeletal muscle.METHODSThe single-blinded crossover counterbalanced study was completed by 12 participants. Participants were randomly divided into either GA (2000 mg of GA) or placebo trials immediately after completing a single bout of cycling exercise at 75% Maximal oxygen uptake (VO_2max) for 60 minutes. Participants consumed either GA (2000 mg) or placebo capsules with a high glycemic index carbohydrate meal (2 g carb/body weight) immediately after exercise. Muscle samples were collected at 0-h and 3-h post-exercise. Muscle samples were used to measure glycogen levels, GLUT4 protein expression, as well as transcription factors for glucose uptake, and mitochondria biogenesis. Plasma glucose, insulin, glycerol, non-esterified fatty acid (NEFA) concentrations, and respiratory exchange ratio (RER) were also analyzed during the post-exercise recovery periods.RESULTSSkeletal muscle glycogen replenishment was significantly elevated during the 3-h recovery period for GA concurrent with no difference in GLUT4 protein expression between the garlic and placebo trials. PGC1-α gene expression was up-regulated for both GA and placebo after exercise (p < 0.05). Transcript factors corresponding to muscle mitochondrial biosynthesis were significantly enhanced under acute garlic supplementation as demonstrated by TFAM and FIS1. However, the gene expression of SIRT1, ERRα, NFR1, NFR2, MFN1, MFN2, OPA1, Beclin-1, DRP1 were not enhanced, nor were there any improvements in GLUT4 expression, following post-exercise garlic supplementation.CONCLUSIONAcute post-exercise garlic supplementation may improve the replenishment of muscle glycogen, but this appears to be unrelated to the gene expression for glucose uptake and mitochondrial biosynthesis in exercised human skeletal muscle.

01 Dec 2024·International Immunopharmacology

Nrf2 mitigates sepsis-associated encephalopathy-induced hippocampus ferroptosis via modulating mitochondrial dynamic homeostasis

Article

Author: Wang, Shun ; Qiu, Zebao ; Wang, Jin ; Yang, Xin ; Li, Zhi ; Duan, Haifeng ; Cai, Shuhan ; Li, Xinyi ; Zhang, Lei

Sepsis-associated encephalopathy (SAE) is a serious neurological complication accompanied with acute and long-term cognitive dysfunction. Ferroptosis is a newly discovered type of cell death that is produced by iron-dependent lipid peroxidation. Emerging evidence suggests that ferroptosis is involved in SAE. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a mitochondria related gene involved in ferroptosis. However, the role of Nrf2 in SAE and the mechanisms remains elusive. In this study, we found that Nrf2 knockout aggravated cognitive and emotional dysfunction and promoted caecal ligation and puncture (CLP)-induced brain injury and hippocampus ferroptosis as indicated by the increase of ROS, Fe²⁺ and the levels of proinflammatory cytokines. Meanwhile, the levels of glutathione peroxidase 4 (GPX4), SLC7A11 and glutathionewere downregulatedin Nrf2 knockout group. In vitro experiments showed that mitochondrial ROS, Fe²⁺ and the expression of Fis1 and Drp1 decreased, and the level of Mfn1 and Opa-1 increased after Nrf2 overexpression. The silence of Nrf2 increased the expression of ROS, MDA and Fe²⁺, while decreased glutathione, mitochondrial membrane potential (MMP) and cell viability in vitro, indicating Nrf2 improved LPS-induced mitochondrial dysfunction and mitigated hippocampal cells ferroptosis. These results suggest that Nrf2 could inhibit ferroptosis and neuroinflammation in hippocampus and reduce cognitive dysfunction in SAE mice, making it a potential therapeutic target in the treatment of SAE. The protective effects of Nrf2 on the brain may be mediated by maintaining mitochondrial dynamic homeostasis.

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FIS1

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