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However, the potential involvement of proteolytic system macroautophagy\/autophagy in this wasting process remains elusive. Autophagy is precisely regulated to maintain cell survival and homeostasis; thus its dysregulation (i.e., overactivation or persistent suppression) could lead to detrimental outcomes in skeletal muscle. Here we show that infusion of ANG II for 7 days in male FVB mice suppressed autophagy in skeletal muscle. ANG II blunted microtubule-associated protein 1 light chain 3B (LC3B)-I-to-LC3B-II conversion (an autophagosome marker), increased p62\/SQSTM1 (an autophagy cargo receptor) protein expression, and decreased the number of autophagic vacuoles. ANG II inhibited UNC-51-like kinase 1 via inhibition of 5\u2032-AMP-activated kinase and activation of mechanistic target of rapamycin complex 1, leading to reduced phosphorylation of beclin-1<jats:sup>Ser14<\/jats:sup> and Autophagy-related protein 14<jats:sup>Ser29<\/jats:sup>, suggesting that ANG II impairs autophagosome formation in skeletal muscle. In line with ANG II-mediated suppression of autophagy, ANG II promoted accumulation of abnormal\/damaged mitochondria, characterized by swelling and disorganized cristae and matrix dissolution, with associated increase in PTEN-induced kinase 1 protein expression. ANG II also reduced mitochondrial respiration, indicative of mitochondrial dysfunction. Together, these results demonstrate that ANG II reduces autophagic activity and disrupts mitochondrial ultrastructure and function, likely contributing to skeletal muscle wasting. Therefore, strategies that activate autophagy in skeletal muscle have the potential to prevent or blunt ANG II-induced skeletal muscle wasting in chronic diseases. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY Our study identified a novel mechanism whereby angiotensin II (ANG II) impairs mitochondrial energy metabolism in skeletal muscle. ANG II suppressed autophagosome formation by inhibiting the UNC-51-like kinase 1(ULK1)-beclin-1 axis, resulting in accumulation of abnormal\/damaged and dysfunctional mitochondria and reduced mitochondrial respiratory capacity. Therapeutic strategies that activate the ULK1-beclin-1 axis have the potential to delay or reverse skeletal muscle wasting in chronic diseases characterized by increased systemic ANG II levels. <\/jats:p>","DOI":"10.1152\/japplphysiol.00898.2018","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T16:03:10Z","timestamp":1554393790000},"page":"1550-1562","source":"Crossref","is-referenced-by-count":28,"title":["Angiotensin II suppresses autophagy and disrupts ultrastructural morphology and function of mitochondria in mouse skeletal muscle"],"prefix":"10.1152","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8230-0012","authenticated-orcid":false,"given":"Kleiton Augusto Santos","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Missouri School of Medicine, Columbia, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaysa","family":"Ghiarone","sequence":"additional","affiliation":[{"name":"Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Cell and Immunobiology Core, University of Missouri, Columbia, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DeAna","family":"Grant","sequence":"additional","affiliation":[{"name":"Electron Microcopy Core Facility, University of Missouri, Columbia, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommi","family":"White","sequence":"additional","affiliation":[{"name":"Electron Microcopy Core Facility, University of Missouri, Columbia, Missouri"},{"name":"Department of Biochemistry, University of Missouri, Columbia, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madlyn I.","family":"Frisard","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy","family":"Sukhanov","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Missouri School of Medicine, Columbia, Missouri"},{"name":"Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bysani","family":"Chandrasekar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Missouri School of Medicine, Columbia, Missouri"},{"name":"Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri"},{"name":"Research Service, Harry S. 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