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Mitophagy

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https://www.readbyqxmd.com/read/28722510/bnip3l-dependent-mitophagy-accounts-for-mitochondrial-clearance-during-three-factors-induced-somatic-cell-reprogramming
#1
Ge Xiang, Liang Yang, Qi Long, Keshi Chen, Haite Tang, Yi Wu, Zihuang Liu, Yanshuang Zhou, Juntao Qi, Lingjun Zheng, Wenbo Liu, Zhongfu Ying, Weimin Fan, Hongyan Shi, Hongmei Li, Xiaobing Lin, Mi Gao, Jinglei Liu, Feixiang Bao, Linpeng Li, Lifan Duan, Min Li, Xingguo Liu
Induced pluripotent stem cells (iPSCs) have less and immature mitochondria than somatic cells and mainly rely on glycolysis for energy source. During somatic cell reprogramming, somatic mitochondria and other organelles get remodeled. However, events of organelle remodeling and interaction during somatic cell reprogramming have not been extensively explored. We show that both SKP/SKO (Sox2, Klf4, Pou5f1/Oct4) and SKPM/SKOM (SKP/SKO plus Myc/c-Myc) reprogramming lead to decreased mitochondrial mass but with different kinetics and by divergent pathways...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28719148/high-expression-of-fundc1-predicts-poor-prognostic-outcomes-and-is-a-promising-target-to-improve-chemoradiotherapy-effects-in-patients-with-cervical-cancer
#2
Hailing Hou, Puchun Er, Jingjing Cheng, Xiuli Chen, Xiaofeng Ding, Yuwen Wang, Xi Chen, Zhiyong Yuan, Qingsong Pang, Ping Wang, Dong Qian
FUN14 domain containing 1 (FUNDC1) is an important molecule in receptor-dependent mitophagy. However, the roles of FUNDC1 in human cancer biology remain unknown. The aim of this study was to explore the expression and roles of FUNDC1 in cervical cancer. Immunohistochemistry and Western blotting were applied to detect the expression of FUNDC1, and small-hairpin RNA was applied to inhibit the expression of endogenous FUNDC1 in cervical cancer cells. MTT assays and Flow cytometric analysis were applied to examine cell proliferation and apoptosis...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28717105/ephedrine-induced-mitophagy-via-oxidative-stress-in-human-hepatic-stellate-cells
#3
Ah Young Lee, Yoonjeong Jang, Seong-Ho Hong, Seung-Hee Chang, Sungjin Park, Sanghwa Kim, Kyung-Sun Kang, Ji-Eun Kim, Myung-Haing Cho
The herb Ephedra sinica (also known as Chinese ephedra or Ma Huang), used in traditional Chinese medicine, contains alkaloids identical to ephedrine and pseudoephedrine as its principal active constituents. Recent studies have reported that ephedrine has various side effects in the cardiovascular and nervous systems. In addition, herbal Ephedra, a plant containing many pharmacologically active alkaloids, principally ephedrine, has been reported to cause acute hepatitis. Many studies reported clinical cases, however, the cellular mechanism of liver toxicity by ephedrine remains unknown...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28704726/bnip3-induction-by-hypoxia-stimulates-fasn-dependent-free-fatty-acid-production-enhancing-therapeutic-potential-of-umbilical-cord-blood-derived-human-mesenchymal-stem-cells
#4
Hyun Jik Lee, Young Hyun Jung, Gee Euhn Choi, So Hee Ko, Sei-Jung Lee, Sang Hun Lee, Ho Jae Han
Mitophagy under hypoxia is an important factor for maintaining and regulating stem cell functions. We previously demonstrated that fatty acid synthase (FASN) induced by hypoxia is a critical lipid metabolic factor determining the therapeutic efficacy of umbilical cord blood-derived human mesenchymal stem cells (UCB-hMSCs). Therefore, we investigated the mechanism of a major mitophagy regulator controlling lipid metabolism and therapeutic potential of UCB-hMSCs. This study revealed that Bcl2/adenovirus E1B 19kDa protein-interacting protein 3 (BNIP3)-dependent mitophagy is important for reducing mitochondrial reactive oxygen species accumulation, anti-apoptosis, and migration under hypoxia...
July 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28703790/a-fluorescence-based-imaging-method-to-measure-in-vitro-and-in-vivo-mitophagy-using-mt-keima
#5
Nuo Sun, Daniela Malide, Jie Liu, Ilsa I Rovira, Christian A Combs, Toren Finkel
Mitophagy is a cellular process that selectively removes damaged, old or dysfunctional mitochondria. Defective mitophagy is thought to contribute to normal aging and to various neurodegenerative and cardiovascular diseases. Previous methods used to detect mitophagy in vivo were cumbersome, insensitive and difficult to quantify. We created a transgenic mouse model that expresses the pH-dependent fluorescent protein mt-Keima in order to more readily assess mitophagy. Keima is a pH-sensitive, dual-excitation ratiometric fluorescent protein that also exhibits resistance to lysosomal proteases...
August 2017: Nature Protocols
https://www.readbyqxmd.com/read/28702322/mitochondrial-transcription-factor-b2-is-essential-for-mitochondrial-and-cellular-function-in-pancreatic-%C3%AE-cells
#6
Lisa M Nicholas, Bérengère Valtat, Anya Medina, Lotta Andersson, Mia Abels, Inês G Mollet, Deepak Jain, Lena Eliasson, Nils Wierup, Malin Fex, Hindrik Mulder
OBJECTIVE: Insulin release from pancreatic β-cells is controlled by plasma glucose levels via mitochondrial fuel metabolism. Therefore, insulin secretion is critically dependent on mitochondrial DNA (mtDNA) and the genes it encodes. Mitochondrial transcription factor B2 (TFB2M) controls transcription of mitochondrial-encoded genes. However, its precise role in mitochondrial metabolism in pancreatic β-cells and, consequently, in insulin secretion remains unknown. METHODS: To elucidate the role of TFB2M in mitochondrial function and insulin secretion in vitro and in vivo, mice with a β-cell specific homozygous or heterozygous knockout of Tfb2m and rat clonal insulin-producing cells in which the gene was silenced were examined with an array of metabolic and functional assays...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28698153/curcumin-prevents-cisplatin-induced-renal-alterations-in-mitochondrial-bioenergetics-and-dynamic
#7
Bibiana Ortega-Domínguez, Omar Emiliano Aparicio-Trejo, Fernando E García-Arroyo, Juan Carlos León-Contreras, Edilia Tapia, Eduardo Molina-Jijón, Rogelio Hernández-Pando, Laura Gabriela Sánchez-Lozada, Diana Barrera-Oviedo, José Pedraza-Chaverri
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model...
July 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28698145/increase-in-proteins-involved-in-mitochondrial-fission-mitophagy-proteolysis-and-antioxidant-response-in-type-i-endometrial-cancer-as-an-adaptive-response-to-respiratory-complex-i-deficiency
#8
Antonella Cormio, Clara Musicco, Giuseppe Gasparre, Gennaro Cormio, Vito Pesce, AnnaMaria Sardanelli, Maria Nicola Gadaleta
Pathogenic mtDNA mutations associated with alterations of respiratory complex I, mitochondrial proliferation (oncocytic-like phenotype) and increase in antioxidant response were previously reported in type I endometrial carcinoma (EC). To evaluate whether in the presence of pathogenic mtDNA mutations other mitochondrial adaptive processes were triggered by cancer cells, the expression level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and complex I deficiency...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28696827/isolation-of-rab5-positive-endosomes-reveals-a-new-mitochondrial-degradation-pathway-utilized-by-bnip3-and-parkin
#9
Babette C Hammerling, Sarah E Shires, Leonardo J Leon, Melissa Q Cortez, Åsa B Gustafsson
Degradation of mitochondria is an important cellular quality control mechanism mediated by two distinct pathways: one involving Parkin-mediated ubiquitination and the other dependent on mitophagy receptors. It is known that mitochondria are degraded by the autophagy pathway; however, we recently reported that the small GTPase Rab5 and early endosomes also participate in Parkin-mediated mitochondrial clearance. Here, we have developed a protocol to isolate Rab5-positive vesicles from cells for proteomics analysis and provide additional data confirming that mitophagy regulators and mitochondrial proteins are present in these vesicles...
July 11, 2017: Small GTPases
https://www.readbyqxmd.com/read/28689991/ubiquitin-phosphorylated-at-ser57-hyper-activates-parkin
#10
Susanna George, Sabrina M Wang, Yumin Bi, Margot Treidlinger, Kathryn R Barber, Gary S Shaw, Patrick O'Donoghue
Malfunction of the ubiquitin (Ub) E3 ligase, parkin, leads to defects in mitophagy and protein quality control linked to Parkinson's disease. Parkin activity is stimulated by phosphorylation of Ub at Ser65 (pUb(S65)). Since the upstream kinase is only known for Ser65 (PINK1), the biochemical function of other phosphorylation sites on Ub remain largely unknown. We used fluorescently labelled and site-specifically phosphorylated Ub substrates to quantitatively relate the position and stoichiometry of Ub phosphorylation to parkin activation...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28688199/differential-expression-of-park2-splice-isoforms-in-an-in-vitro-model-of-dopaminergic-like-neurons-exposed-to-toxic-insults-mimicking-parkinson-s-disease
#11
Valentina La Cognata, Grazia Maugeri, Agata Grazia D'Amico, Salvatore Saccone, Concetta Federico, Sebastiano Cavallaro, Velia D'Agata
Mutations in PARK2 (or parkin) are responsible for 50% of cases of autosomal-recessive juvenile-onset Parkinson's disease (PD). To date, 21 alternative splice variants of the human gene have been cloned. Yet most studies have focused on the full-length protein, whereas the spectrum of the parkin isoforms expressed in PD has never been investigated. In this study, the role of parkin proteins in PD neurodegeneration was explored for the first time by analyzing their expression profile in an in vitro model of PD...
July 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28686226/myc-is-a-positive-regulator-of-choline-metabolism-and-impedes-mitophagy-dependent-necroptosis-in-diffuse-large-b-cell-lymphoma
#12
J Xiong, L Wang, X-C Fei, X-F Jiang, Z Zheng, Y Zhao, C-F Wang, B Li, S-J Chen, A Janin, R P Gale, W-L Zhao
The activation of oncogenes can reprogram tumor cell metabolism. Here, in diffuse large B-cell lymphoma (DLBCL), serum metabolomic analysis revealed that oncogenic MYC could induce aberrant choline metabolism by transcriptionally activating the key enzyme phosphate cytidylyltransferase 1 choline-α (PCYT1A). In B-lymphoma cells, as a consequence of PCYT1A upregulation, MYC impeded lymphoma cells undergo a mitophagy-dependent necroptosis. In DLBCL patients, overexpression of PCYT1A was in parallel with an increase in tumor MYC, as well as a decrease in serum choline metabolite phosphatidylcholine levels and an International Prognostic Index, indicating intermediate-high or high risk...
July 7, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28685977/the-post-therapeutic-effect-of-rapamycin-in-mild-traumatic-brain-injured-rats-ensuing-in-the-upregulation-of-autophagy-and-mitophagy
#13
Changxing Wang, Zhiying Hu, Yang Zou, Mingjun Xiang, Yuting Jiang, Benson O A Botchway, Xue Huo, Xiaoxue Du, Marong Fang
Mild traumatic brain injury (mTBI), common in juveniles, has been reported to be caused by sports-related concussion. Many young children may suffer from post-concussion syndrome. mTBI, in early stages of life, could play a part in neuron apoptosis and degeneration, cognitive and motor coordination impairment, as well as dementia. Our study was aimed at further investigating the post therapeutic efficacy of rapamycin in the recuperation of mTBI whiles at the same time investigating the metamorphosis in both autophagy and mitophagy in mTBI...
July 7, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28685325/potential-signaling-pathways-of-acute-endurance-exercise-induced-cardiac-autophagy-and-mitophagy-and-its-possible-role-in-cardioprotection
#14
REVIEW
Youngil Lee, Insu Kwon, Yongchul Jang, Wankeun Song, Ludmila M Cosio-Lima, Mark H Roltsch
Cardiac myocytes are terminally differentiated cells and possess extremely limited regenerative capacity; therefore, preservation of mature cardiac myocytes throughout the individual's entire life span contributes substantially to healthy living. Autophagy, a lysosome-dependent cellular catabolic process, is essential for normal cardiac function and mitochondria maintenance. Therefore, it may be reasonable to hypothesize that if endurance exercise promotes cardiac autophagy and mitochondrial autophagy or mitophagy, exercise-induced cardiac autophagy (EICA) or exercise-induced cardiac mitophagy (EICM) may confer propitious cellular environment and thus protect the heart against detrimental stresses, such as an ischemia-reperfusion (I/R) injury...
July 6, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28684113/sericin-improves-heart-and-liver-mitochondrial-architecture-in-hypercholesterolaemic-rats-and-maintains-pancreatic-and-adrenal-cell-biosynthesis
#15
Sumate Ampawong, Duangnate Isarangkul, Pornanong Aramwit
Hypercholesterolaemia is well known to be associated with mitochondrial dysfunction, subsequently leading to multiple organ failure. Similar to other natural products, sericin is a candidate for adjunctive therapy in hyperlipidaemic conditions. However, the cholesterol-lowering mechanisms of sericin are multifactorial and controversial. Here, a high-cholesterol-fed rat model with or without sericin treatment was established using a dosage of 1,000mg/kg/day for 30 days. Blood lipid profiles, oxidative stress markers (superoxide dismutase, SOD; malondialdehyde, MDA; nuclear factor erythroid 2-related factor, Nrf-2), dysmorphic mitochondria in relation to fission (dynamin-related protein-1; Drp-1) and fusion (guanosine triphosphatase mutated in dominant optic atrophy; OPA-1) markers and biosynthetic markers (aquaporin, AQP-1; tubulin-4β, Tb4B) in the pancreas and adrenal gland were evaluated...
July 3, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28682452/mitochondrial-dysfunction-and-potential-anticancer-therapy
#16
REVIEW
Matilde E Lleonart, Robert Grodzicki, Dmitri M Graifer, Alex Lyakhovich
Mitochondrial dysfunction (MDF) has been identified as an important factor in various diseases ranging from neurological disorders, to diseases of the cardiovascular system and metabolic syndromes. MDF was also found in cancer as well as in cancer predisposition syndromes with defective DNA damage response (DDR) machinery. Moreover, a recent highlight arises from the detection of MDF in eukaryotic cells upon treatment with antibiotics. In this review, we focus on recent studies of MDF in pathological conditions with a particular emphasis on the effects of various classes of antibiotics on mitochondria...
July 6, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28681509/akt2-ablation-prolongs-life-span-and-improves-myocardial-contractile-function-with-adaptive-cardiac-remodeling-role-of-sirt1-mediated-autophagy-regulation
#17
Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F Ceylan, Wei Guo, Jian Yang, Yingmei Zhang
Aging is accompanied with unfavorable geometric and functional changes in the heart involving dysregulation of Akt and autophagy. This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca(2+) properties were evaluated using echocardiography, IonOptix(®) edge-detection and fura-2 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28679997/alternative-autophagy-plays-a-central-role-in-mitochondria-elimination-from-reticulocytes
#18
Shigeomi Shimizu
Mitophagy is a mitochondrial quality control mechanism where damaged and surplus mitochondria are degraded by macroautophagy. Mitophagy is associated with various physiological and pathological events such as mitochondrial clearance during the terminal differentiation of reticulocytes. There are two different mammalian autophagy pathways: the Atg5-dependent conventional pathway and Atg5-independent alternative pathway; the latter is involved in reticulocyte's mitophagy.
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28673964/sorafenib-targets-the-mitochondrial-electron-transport-chain-complexes-and-atp-synthase-to-activate-the-pink1-parkin-pathway-and-modulate-cellular-drug-response
#19
Conggang Zhang, Zeyu Liu, Eric Bunker, Adrian Ramirez, Schuyler Lee, Yinghua Peng, Aik Choon Tan, S Gail Eckhardt, Douglas A Chapnick, Xuedong Liu
Sorafenib (Nexavar) is a broad-spectrum multi-kinase inhibitor that proves effective in treating advanced renal-cell carcinoma and liver cancer. Despite its well-characterized mechanism of action on several established cancer-related protein kinases, sorafenib causes variable responses among human tumors, although the cause for this variation is unknown. In an unbiased screening of an oncology drug library, we found that sorafenib activates recruitment of the ubiquitin E3 ligase Parkin to damaged mitochondria...
July 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28673704/spinal-cord-ischemia-reperfusion-injury-micrornas-and-mitophagy-at-a-crossroads
#20
EDITORIAL
Leora B Balsam
No abstract text is available yet for this article.
June 10, 2017: Journal of Thoracic and Cardiovascular Surgery
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