Last update 19 Sep 2024

FIS1

Last update 19 Sep 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

891

Literatures (Medical) associated with FIS1

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·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Oleanonic acid ameliorates mutant Aβ precursor protein-induced oxidative stress, autophagy deficits, ferroptosis, mitochondrial damage, and ER stress in vitro

Article

Author: Wang, Yicheng ; Zhou, Dongming ; Zhang, Heng ; Wang, Hongyan ; Tao, Liqing ; Liu, Zewang ; Li, Xinying

Accumulation in the brain of amyloid-β (Aβ), derived from cleavage of Aβ precursor protein (APP), is a hallmark of Alzheimer's disease (AD). Oleanonic acid (OA), a phytochemical from several plants, has proven anti-inflammatory effects, but its role in AD remains unknown. Here we found that OA reduced APP expression and inhibited oxidative stress via Nrf2/HO-1 signaling in SH-SY5Y neuroblastoma cells stably overexpressing APP. OA suppressed phosphorylated mTOR but increased autophagy markers ATG5 and LC3-II. Moreover, OA rescued ferroptosis-related factors GPX4, NCOA, and COX2 and ER stress markers GRP78, CHOP, and three main induction pathways of ER stress including IRE1/XBP1s, PERK/EIF2α, and ATF6. OA alleviated mitochondrial damage through MFN1, MFN2, OPA1, FIS1, and DRP1. Furthermore, OA upregulated GDF11 expression and downregulated phosphorylation of ErbB4 and TrkB without affecting BDNF levels. Thus, OA might protect neurons from APP-induced neurotoxicity by inhibiting oxidative stress, autophagy deficits, ferroptosis, mitochondrial damage, and ER stress in AD, providing a new promising therapeutic strategy in patients with AD.

01 Oct 2024·Experimental Gerontology

Contribution of impaired autophagy, mitochondrial dysfunction and abnormal lipolysis to epididymal aging in mice

Article

Author: Wu, Chongkang ; Lv, Zhengmei ; Liu, Chao ; Zhang, Shoubing

With the increase of the aged population in modern society, research on aging and aging-related diseases has attracted increasing attention. Unlike women, men experience changes gradually in the reproductive system during aging. The epididymis is an important organ for sperm maturation and storage, but less study has been conducted to investigate cellular senescence in aging epididymis and the corresponding influences on sperm. This study aims to explore cellular and molecular mechanisms underlying aging changes in epididymal tissues. Cellular senescence in the epididymis of 18-month-old C57BL/6 J mice was evaluated with SA (senescence-associated)-β-galactosidase staining and molecular markers such as P21 and Lamin B, compared to the 2-month-old young group. Western blot analysis and immunofluorescence staining were performed to examine the proteins expressions involved in AMPKα/SIRT1 pathway, autophagy/mitophagy, mitochondrial dynamics and lipolysis. The results showed that in old mice AMPKα/ SIRT1 pathway was downregulated with increased acetylation in the epididymal tissues. Reduced expressions of autophagy related genes and PINK1/PARK2 were detected as well as increased P62 protein level and decreased colocalization of LC3 and LAMP2, which indicated deficient autophagy and mitophagy occurred in aging epididymal tissues. Significant decreased expressions of MFN1, MFN2, p-DRP1(Ser637) and FIS1 showed an imbalance in mitochondrial dynamics in aging epididymal tissues. Additionally, intracellular lipid droplets accumulation occurred in epididymal epithelial cells in old mice, with reduced expressions of the lipolysis enzymes ATGL, HSL and Ascl4. Lipophagy impairment was further detected by minimal colocalization of lipid droplets with either LC3 or LAMP2 in the epididymal ductal epithelial cells of old mice. Our study provides new insights into the molecular mechanisms of impaired autophagy, imbalanced mitochondrial dynamics and disrupted lipolysis, which together contribute to senescent changes and may be detrimental to the epididymal function during aging.

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FIS1

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