{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:53:48Z","timestamp":1793836428557,"version":"4.6.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NUTRIM Graduate programme"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Iron homeostasis is essential for mitochondrial function, and iron deficiency has been associated with skeletal muscle weakness and decreased exercise capacity in patients with different chronic disorders. We hypothesized that iron deficiency\u2010induced loss of skeletal muscle mitochondria is caused by increased mitochondrial clearance. To study this, C2C12 myotubes were subjected to the iron chelator deferiprone. Mitochondrial parameters and key constituents of mitophagy pathways were studied in presence or absence of pharmacological autophagy inhibition or knockdown of mitophagy\u2010related proteins. Furthermore, it was explored if mitochondria were present in extracellular vesicles (EV). Iron chelation resulted in an increase in BCL2\/Adenovirus E1B 19\u00a0kDa protein\u2010interacting protein 3 (BNIP3) and BNIP3\u2010like gene and protein levels, and the appearance of mitochondria encapsulated by lysosome\u2010like vesicular structures in myotubes. Moreover, mitochondria were secreted via EV. These changes were associated with cellular mitochondrial impairments. These impairments were unaltered by autophagy inhibition, knockdown of mitophagy\u2010related proteins BNIP3 and BNIP3L, or knockdown of their upstream regulator hypoxia\u2010inducible factor 1 alpha. In conclusion, mitophagy is not essential for development of iron deficiency\u2010induced reductions in mitochondrial proteins or respiratory capacity. The secretion of mitochondria\u2010containing EV could present an additional pathway via which mitochondria can be cleared from iron chelation\u2010exposed myotubes.<\/jats:p>","DOI":"10.1096\/fj.201901815r","type":"journal-article","created":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T06:32:32Z","timestamp":1584945152000},"page":"6703-6717","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Iron deficiency\u2010induced loss of skeletal muscle mitochondrial proteins and respiratory capacity; the role of mitophagy and secretion of mitochondria\u2010containing vesicles"],"prefix":"10.1096","volume":"34","author":[{"given":"Pieter A.","family":"Leermakers","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+ Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H. V.","family":"Remels","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre+ Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke I.","family":"Zonneveld","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy GROW School for Oncology and Developmental Biology Maastricht University Medical Centre+ Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper M. A.","family":"Rouschop","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy GROW School for Oncology and Developmental Biology Maastricht University Medical Centre+ Maastricht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemie M. W. 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