Редактирование: FIS1 (раздел)

==Publications==

{{medline-entry
|title=Alterations in Mitochondrial Dynamic-related Genes in the Peripheral Blood of Alzheimer's Disease Patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/33023448
|abstract=Mitochondrial dysfunction is a pathological feature that manifests early in the brains of patients with Alzheimer's Disease (AD). The disruption of mitochondrial dynamics contributes to mitochondrial morphological and functional impairments. Our previous study demonstrated that the expression of genes involved in amyloid beta generation was altered in the peripheral blood of AD patients. The aim of this study was to further investigate the relative levels of mitochondrial genes involved in mitochondrial dynamics, including mitochondrial fission and fusion, and mitophagy in peripheral blood samples from patients with AD compared to healthy controls. The mRNA levels were analyzed by real-time polymerase chain reaction. Gene expression profiles were assessed in relation to cognitive performance. Significant changes were observed in the mRNA expression levels of fission-related genes; Fission1 ([[FIS1]]) levels in AD subjects were significantly higher than those in healthy controls, whereas Dynamin- related protein 1 (DRP1) expression was significantly lower in AD subjects. The levels of the mitophagy-related genes, [[PTEN]]-induced kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3), were significantly increased in AD subjects and elderly controls compared to healthy young controls. The mRNA levels of Parkin (PARK2) were significantly decreased in AD. Correlations were found between the expression levels of [[FIS1]], DRP1 and PARK2 and cognitive performance scores. Alterations in mitochondrial dynamics in the blood may reflect impairments in mitochondrial functions in the central and peripheral tissues of AD patients. Mitochondrial fission, together with mitophagy gene profiles, might be potential considerations for the future development of blood-based biomarkers for AD.

|keywords=* Alzheimer's disease
* DRP1
* FIS1
* aging
* mitochondrial dynamics
* mitophagy
|full-text-url=https://sci-hub.do/10.2174/1567205017666201006162538
}}
{{medline-entry
|title=A mitochondrial [[FUNDC1]]/HSC70 interaction organizes the proteostatic stress response at the risk of cell morbidity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30591555
|abstract=Both protein quality and mitochondrial quality are vital for the cellular activity, and impaired proteostasis and mitochondrial dysfunction are common etiologies of aging and age-related disorders. Here, we report that the mitochondrial outer membrane protein [[FUNDC1]] interacts with the chaperone HSC70 to promote the mitochondrial translocation of unfolded cytosolic proteins for degradation by [[LONP1]] or for formation of non-aggresomal mitochondrion-associated protein aggregates (MAPAs) upon proteasome inhibition in cultured human cells. Integrative approaches including csCLEM, Apex, and biochemical analysis reveal that MAPAs contain ubiquitinated cytosolic proteins, autophagy receptor p62, and mitochondrial proteins. MAPAs are segregated from mitochondria in a [[FIS1]]-dependent manner and can subsequently be degraded via autophagy. Although the [[FUNDC1]]/HSC70 pathway promotes the degradation of unfolded cytosolic proteins, excessive accumulation of unfolded proteins on the mitochondria prior to MAPA formation impairs mitochondrial integrity and activates AMPK, leading to cellular senescence. We suggest that human mitochondria organize cellular proteostatic response at the risk of their own malfunction and cell lethality.
|mesh-terms=* ATP-Dependent Proteases
* Autophagy
* Cell Hypoxia
* Cellular Senescence
* Cytosol
* HEK293 Cells
* HSC70 Heat-Shock Proteins
* Humans
* Membrane Proteins
* Microtubule-Associated Proteins
* Mitochondria
* Mitochondrial Membranes
* Mitochondrial Proteins
* Mitophagy
* Phosphorylation
* Protein Binding
* Proteostasis
* Stress, Physiological
|keywords=* cellular senescence
* mitochondria
* mitochondrial quality control
* mitophagy
* proteostatic stress
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356068
}}
{{medline-entry
|title=Increased Degradation Rates in the Components of the Mitochondrial Oxidative Phosphorylation Chain in the Cerebellum of Old Mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29503614
|abstract=Brain structures differ in the magnitude of age-related neuron loss with the cerebellum being more affected. An underlying cause could be an age-related decline in mitochondrial bioenergetics. Successful aging of mitochondria reflects a balanced turnover of proteins involved in mitochondrial biogenesis and mitophagy. Thus, an imbalance in mitochondrial turnover can contribute to the diminution of cellular function seen during aging. Mitochondrial biogenesis and mitophagy are mediated by a set of proteins including [[MFN1]], [[MFN2]], [[OPA1]], DRP1, [[FIS1]] as well as DMN1l and [[DNM1]], all of which are required for mitochondrial fission. Using N15 labeling, we report that the turnover rates for DMN1l and [[FIS1]] go in opposite directions in the cerebellum of 22-month-old C57BL6j mice as compared to 3-month-old mice. Previous studies have reported decreased turnover rates for the mitochondrial respiratory complexes of aged rodents. In contrast, we found increased turnover rates for mitochondrial proteins of the oxidative phosphorylation chain in the aged mice as compared to young mice. Furthermore, the turnover rate of the components that are most affected by aging -complex III components ([i]ubiquinol cytochrome C oxidoreductase[/i]) and complex IV components ([i]cytochrome C oxidase[/i])- was significantly increased in the senescent cerebellum. However, the turnover rates of proteins involved in mitophagy (i.e., the proteasomal and lysosomal degradation of damaged mitochondria) were not significantly altered with age. Overall, our results suggest that an age-related imbalance in the turnover rates of proteins involved in mitochondrial biogenesis and mitophagy (DMN1l, [[FIS1]]) in conjunction with an age-related imbalance in the turnover rates of proteins of the complexes III and IV of the electron transfer chain, might impair cerebellar mitochondrial bioenergetics in old mice.

|keywords=* aging
* cerebellum
* mice
* mitochondria
* proteins
* turnover
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820363
}}
{{medline-entry
|title=Proteomics and metabolomics identify molecular mechanisms of aging potentially predisposing for chronic lymphocytic leukemia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29196338
|abstract=B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, the chronic B cell leukemia cell line JVM-13 was also included. A principal component analysis comprising 6,945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells. Mass spectrometric proteomics data have been made fully accessible via ProteomeXchange with identifier PXD006570-PXD006572, PXD006576, PXD006578, and PXD006589-PXD006591. Remarkably, B cells from aged controls displayed significant regulation of proteins related to stress management in mitochondria and ROS stress such as [[DLAT]], [[FIS1]], and [[NDUFAB1]], and DNA repair, including [[RAD9A]], [[MGMT]], and [[XPA]]. ROS levels were indeed found significantly increased in B cells but not in T cells or monocytes from aged individuals. These alterations may be relevant for tumorigenesis and were observed similarly in B-CLL cells. In B-CLL cells, some remarkable unique features like the loss of tumor suppressor molecules [[PNN]] and [[JARID2]], the stress-related serotonin transporter [[SLC6A4]], and high expression of [[ZNF207]], [[CCDC88A]], [[PIGR]] and [[ID3]], otherwise associated with stem cell phenotype, were determined. Alterations of metabolic enzymes were another outstanding feature in comparison to normal B cells, indicating increased beta-oxidation of fatty acids and increased consumption of glutamine. Targeted metabolomics assays corroborated these results. The present findings identify a potential proteome signature for immune senescence in addition to previously unrecognized features of B-CLL cells and suggest that aging may be accompanied by cellular reprogramming functionally relevant for predisposing B cells to transform to B-CLL cells.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* B-Lymphocytes
* Cell Line, Tumor
* Female
* Humans
* Leukemia, Lymphocytic, Chronic, B-Cell
* Male
* Metabolomics
* Middle Aged
* Neoplasm Proteins
* Proteomics

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795392
}}
{{medline-entry
|title=Effects of β-hydroxy-β-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28705993
|abstract=Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during BR and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids. Nineteen older adults (60-76 yr) completed 10 days BR followed by 8-wk RT rehabilitation. Subjects were randomized to either HMB (3 g/day HMB; [i]n[/i] = 11) or control (CON; [i]n[/i] = 8) groups. Skeletal muscle cross-sectional area (CSA) was determined by histology from percutaneous vastus lateralis biopsies. We measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission ([[MFN2]], [[OPA1]], [[FIS1]], and DRP1), autophagy (Beclin1, LC3B, and [[BNIP3]]), and atrophy [poly-ubiquinated proteins (poly-ub)] by Western blot. Fatty acid composition of several lipid classes in skeletal muscle was measured by infusion-MS analysis. Poly-ub proteins and OXPHOS complex I increased in both groups following BR ([i]P[/i] < 0.05, main effect for time), and muscle triglyceride content tended to increase following BR in the HMB group ([i]P[/i] = 0.055). RT rehabilitation increased OXPHOS complex II protein ([i]P[/i] < 0.05), and total OXPHOS content tended ([i]P[/i] = 0.0504) to be higher in HMB group. In addition, higher levels of DRP1 and [[MFN2]] were maintained in the HMB group after RT ([i]P[/i] < 0.05). [[BNIP3]] and poly-ub proteins were significantly reduced following rehabilitation in both groups ([i]P[/i] < 0.05). Collectively, these data suggest that HMB influences mitochondrial dynamics and lipid metabolism during disuse atrophy and rehabilitation.  Mitochondrial content and dynamics remained unchanged over 10 days of BR in older adults. HMB stimulated intramuscular lipid storage as triacylglycerol following 10 days of bed rest (BR) and maintained higher mitochondrial OXPHOS content and dynamics during the 8-wk resistance exercise rehabilitation program.
|mesh-terms=* Age Factors
* Aged
* Autophagy
* Bed Rest
* Double-Blind Method
* Energy Metabolism
* Female
* Humans
* Lipid Metabolism
* Male
* Middle Aged
* Mitochondria, Muscle
* Mitochondrial Dynamics
* Mitochondrial Proteins
* Prospective Studies
* Proteolysis
* Quadriceps Muscle
* Resistance Training
* Sarcopenia
* Signal Transduction
* Time Factors
* Treatment Outcome
* Valerates
|keywords=* HMB
* aging
* bed rest
* exercise
* mitochondria
|full-text-url=https://sci-hub.do/10.1152/japplphysiol.00192.2017
}}
{{medline-entry
|title=Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27993601
|abstract=Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, [[OPA1]] and mitofusins, and fission, DRP1 and [[FIS1]], emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus.
|mesh-terms=* AMP-Activated Protein Kinases
* Aging
* Animals
* Dynamins
* GTP Phosphohydrolases
* Humans
* Membrane Proteins
* Microtubule-Associated Proteins
* Mitochondria
* Mitochondrial Proteins
* Obesity
* Sirtuins
* TOR Serine-Threonine Kinases
|keywords=* Ageing
* Fat
* Gender
* Inflammation
* Mitochondria
|full-text-url=https://sci-hub.do/10.1016/j.mad.2016.12.005
}}
{{medline-entry
|title=Inhibition of peroxisome fission, but not mitochondrial fission, increases yeast chronological lifespan.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25840089
|abstract=Mitochondria are key players in aging and cell death. It has been suggested that mitochondrial fragmentation, mediated by the Dnm1/Fis1 organelle fission machinery, stimulates aging and cell death. This was based on the observation that Saccharomyces cerevisiae Δdnm1 and Δfis1 mutants show an enhanced lifespan and increased resistance to cell death inducers. However, the Dnm1/Fis1 fission machinery is also required for peroxisome division. Here we analyzed the significance of peroxisome fission in yeast chronological lifespan, using yeast strains in which fission of mitochondria was selectively blocked. Our data indicate that the lifespan extension caused by deletion of [[FIS1]] is mainly due to a defect in peroxisome fission and not caused by a block in mitochondrial fragmentation. These observations are underlined by our observation that deletion of [[FIS1]] does not lead to lifespan extension in yeast peroxisome deficient mutant cells. 
|mesh-terms=* GTP Phosphohydrolases
* Longevity
* Microscopy, Fluorescence
* Mitochondrial Dynamics
* Mitochondrial Proteins
* Peroxisomes
* Reactive Oxygen Species
* Saccharomyces cerevisiae
* Saccharomyces cerevisiae Proteins
|keywords=* Fis1
* chronological aging
* fission
* mitochondria
* peroxisome
* yeast
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614869
}}