{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:21:51Z","timestamp":1792264911524,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chromium (Cr) compounds are markedly toxic and carcinogenic. Previously, we found that Cr (VI) induced autophagy in A549 cells. Here, the effect of mitochondrial dysfunction and endoplasmic reticulum (ER) stress on inducing mitophagy was investigated in both A549 and H1299 cells. Exposure to Cr (VI) for 6 h significantly enhanced reactive oxygen species (ROS) production and reduced mitochondrial membrane potential (MMP). Transmission electron microscopy showed that Cr (VI) induced mitochondrial morphological changes, such as, mitochondrial swelling and vacuolization. The elevated expression of GRP78 and p\u2010PERK suggested that Cr (VI) resulted in ER stress. Both mitochondrial dysfunction and ER stress played an important role in Cr (VI)\u2010induced mitophagy, as the mitochondrial function inhibitor, carbonyl cyanide 3\u2010chlorophenylhydrazone (CCCP) induced PINK1 and PARK2 and increased the expression of GRP78 and p\u2010PERK while the levels of Cr (VI)\u2010induced PINK1, PARK2, LC3\u2010II were reduced after ER stress inhibitor, phenylbutyric acid (4PBA) pretreatment. When A549 cells were treated with CCCP and 4\u2010PBA simultaneously, CCCP\u2010induced expressions of PINK1, PARK2 and LC3\u2010II decreased significantly compared with that of only CCCP\u2010treated cells, indicating that there was a crosstalk between mitochondria and ER in inducing mitophagy. Additionally, the crosstalk between mitochondrial dysfunction and ER stress modulated the expression of Cr (VI)\u2010induced ATF4, which resulted in mitophagy. Collectively, our data demonstrated that Cr (VI)\u2010induced mitophagy mediated by ATF4 via the crosstalk between ER stress and mitochondrial dysfunction.<\/jats:p>","DOI":"10.1002\/tox.23115","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T07:10:34Z","timestamp":1614669034000},"page":"1162-1172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The crosstalk between mitochondrial dysfunction and endoplasmic reticulum stress promoted\n                    <scp>ATF4<\/scp>\n                    \u2010mediated mitophagy induced by hexavalent chromium"],"prefix":"10.1002","volume":"36","author":[{"given":"Mongameli B.","family":"Dlamini","sequence":"first","affiliation":[{"name":"Department of Occupational and Environmental Health Dalian Medical University  Dalian 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