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This study characterized sublobular respiration and distribution of mtDepo and mitophagy after acute EtOH. C57BL\/6J and GFP-LC3 transgenic mice were gavaged with 6\u2009g\/kg EtOH or vehicle and administered MitoTracker Red (MTR). Hepatocytes were zonally sorted by MTR fluorescence for assessment of oxygen consumption rates (OCRs). Cytochrome P4502E1 (CYP2E1) immunolabeling identified central halves of liver lobules. After vehicle, MTR localized to mitochondria throughout lobules, indicating polarization, with higher OCRs in periportal (PP) hepatocytes compared with pericentral (PC). After EtOH, MTR fluorescence became diffuse in CYP2E1-positive central halves of lobules, signifying mtDepo, whereas portal halves remained polarized. GFP-LC3 puncta marking mitophagy also increased predominantly in central halves. Surface hepatocytes accessible by multiphoton microscopy were CYP2E1-positive and developed mtDepo and GFP-LC3 puncta after EtOH. After hepatocyte isolation, mtDepo reversed shown by rhodamine 123 uptake. At 6\u2009h post-EtOH, OCRs approximately doubled in both PP and PC hepatocytes, returning to baseline by 24\u2009h, but PC displayed greater proportional increases. Acute EtOH induces mtDepo and mitophagy predominantly in central halves of lobules, including within &amp;lt;50\u00a0\u03bcm of the liver surface. Although mtDepo reverses after isolation, elevated respiratory capacity persists. Due to central half mtDepo, PP and PC hepatocytes contribute about equally to the respiratory burst after EtOH.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag013","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:40:56Z","timestamp":1770295256000},"source":"Crossref","is-referenced-by-count":0,"title":["Zonal hepatocellular responses to acute ethanol consumption: impacts on mitochondrial function and liver metabolism"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-9200","authenticated-orcid":false,"given":"Matthew T","family":"Savoca","sequence":"first","affiliation":[{"name":"Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina , Charleston, SC 29425,","place":["United 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