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Timely phagocytosis and clearance of pathogens by macrophages are important in controlling inflammation and alleviating ARDS. However, the precise mechanism of macrophage phagocytosis remains to be explored. Here, we show that the\u00a0expression of Rab26 is increased in\n                    <jats:italic>Escherichia\u2009coli<\/jats:italic>\n                    \u2010 or\n                    <jats:italic>Pseudomonas\u2009aeruginosa<\/jats:italic>\n                    \u2010stimulated bone marrow\u2010derived macrophages. Knocking out Rab26 reduced phagocytosis and bacterial clearance by macrophages. Rab26 interacts with mitochondrial fusion protein mitofusin\u20102 (MFN2) and affects mitochondrial reactive oxygen species generation by regulating MFN2 transport. The levels of MFN2 in mitochondria were reduced in Rab26\u2010deficient bone marrow\u2010derived macrophages, and the levels of mitochondrial reactive oxygen species and ATP were significantly decreased. Knocking down MFN2 using small interfering RNA resulted in decreased phagocytosis and killing ability of macrophages. Rab26 knockout reduced phagocytosis and bacterial clearance by macrophages\n                    <jats:italic>in\u2009vivo<\/jats:italic>\n                    , significantly increased inflammatory factors, aggravated lung tissue damage, and increased mortality in mice. Our results demonstrate that Rab26 regulates phagocytosis and clearance of bacteria by mediating the transport of MFN2 to mitochondria in macrophages, thus alleviating ARDS in mice and potentially in humans.\n                  <\/jats:p>","DOI":"10.1111\/febs.16793","type":"journal-article","created":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T04:59:28Z","timestamp":1681534768000},"page":"4023-4039","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Rab26 promotes macrophage phagocytosis through regulation of MFN2 trafficking to mitochondria"],"prefix":"10.1111","volume":"290","author":[{"given":"Di","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Diseases, Xinqiao Hospital Third Military Medical University (Army Medical University)  Chongqing 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