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Metformin, widely recommended in the management of T2DM, exerts its pleiotropic effects via 5\u02b9\u2010AMP\u2013activated protein kinase (AMPK); however, its effect on mitophagy remains elusive. Recent evidence demonstrates that peripheral blood mononuclear cells (PBMCs) express insulin receptors and the human organic cation transporter protein, and they are extensively being used as a surrogate for examining mitochondrial function in T2DM. Metformin treatment increased the formation of acidic vesicles and mitophagosomes, upregulated mitophagy markers, and enhanced mitophagic flux, as indicated by increased LC3\u2010II expression and reduced p62 protein levels. In addition, pretreatment with compound C (an AMPK inhibitor) significantly decreased the expression of mitophagy markers in metformin\u2010treated cells, indicating that metformin induces mitophagy via the AMPK pathway. In conclusion, metformin\u2010induced mitophagy may improve cellular function, including in \u03b2 cells, by restoring normal mitochondrial phenotype, which may prove beneficial in patients with T2DM and other mitochondrial\u2010related diseases. Moreover, PBMCs may be used as a novel diagnostic biomarker for identifying mitochondrial disorders.<\/jats:p>","DOI":"10.1111\/nyas.14141","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T09:34:34Z","timestamp":1561109674000},"page":"23-36","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Metformin promotes mitophagy in mononuclear cells: a potential <i>in vitro<\/i> model for unraveling metformin's mechanism of action"],"prefix":"10.1111","volume":"1463","author":[{"given":"Shipra","family":"Bhansali","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine and Biotechnology Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Bhansali","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9464-1033","authenticated-orcid":false,"given":"Veena","family":"Dhawan","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Biotechnology Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.165472"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2013.00037"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.47.29911"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/354914"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1071760"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.5402\/2012\/926160"},{"key":"e_1_2_8_8_1","article-title":"The emerging role of proteolysis in mitochondrial quality control and the etiology of Parkinson's disease","volume":"2012","author":"Shanbhag R.","year":"2012","journal-title":"Parkinsons Dis."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110386"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-102808-114910"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/embr.201438501"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2010.04.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.07.006"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00347"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.04.002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1255\/ejms.1285"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.131482"},{"key":"e_1_2_8_18_1","first-page":"77","article-title":"Separation of Leucocytes from blood and bone marrow","volume":"21","author":"Boyum A.","year":"1968","journal-title":"Scand. 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