Journal article
Involvement of the mitochondrial permeability transition pore in chronic ethanol-mediated liver injury in mice
American journal of physiology: Gastrointestinal and liver physiology, Vol.306(4), pp.G265-G277
02/15/2014
DOI: 10.1152/ajpgi.00278.2013
PMCID: PMC3920122
PMID: 24356880
Abstract
Chronic ethanol consumption increases sensitivity of the mitochondrial permeability transition (MPT) pore induction in liver. Ca2+ promotes MPT pore opening, and genetic ablation of cyclophilin D (CypD) increases the Ca2+ threshold for the MPT. We used wild-type (WT) and CypD-null (CypD−/−) mice fed a control or an ethanol-containing diet to investigate the role of the MPT in ethanol-mediated liver injury. Ca2+-mediated induction of the MPT and mitochondrial respiration were measured in isolated liver mitochondria. Steatosis was present in WT and CypD−/− mice fed ethanol and accompanied by increased terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive nuclei. Autophagy was increased in ethanol-fed WT mice compared with ethanol-fed CypD−/− mice, as reflected by an increase in the ratio of microtubule protein 1 light chain 3B II to microtubule protein 1 light chain 3B I. Higher levels of p62 were measured in CypD−/− than WT mice. Ethanol decreased mitochondrial respiratory control ratios and select complex activities in WT and CypD−/− mice. Ethanol also increased CypD protein in liver of WT mice. Mitochondria from control- and ethanol-fed WT mice were more sensitive to Ca2+-mediated MPT pore induction than mitochondria from their CypD−/− counterparts. Mitochondria from ethanol-fed CypD−/− mice were also more sensitive to Ca2+-induced swelling than mitochondria from control-fed CypD−/− mice but were less sensitive than mitochondria from ethanol-fed WT mice. In summary, CypD deficiency was associated with impaired autophagy and did not prevent ethanol-mediated steatosis. Furthermore, increased MPT sensitivity was observed in mitochondria from ethanol-fed WT and CypD−/− mice. We conclude that chronic ethanol consumption likely lowers the threshold for CypD-regulated and -independent characteristics of the ethanol-mediated MPT pore in liver mitochondria.
Details
- Title: Subtitle
- Involvement of the mitochondrial permeability transition pore in chronic ethanol-mediated liver injury in mice
- Creators
- Adrienne L King - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AlabamaTelisha M Swain - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AlabamaZhengkuan Mao - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AlabamaUduak S Udoh - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AlabamaClaudia R Oliva - Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama; andAngela M Betancourt - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, AlabamaCorrine E Griguer - Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama; andDavid R Crowe - Department of Pathology, University of Alabama at Birmingham, Birmingham, AlabamaMathieu Lesort - Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AlabamaShannon M Bailey - Department of Environmental Health Sciences, University of Alabama at Birmingham, Birmingham, Alabama
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: Gastrointestinal and liver physiology, Vol.306(4), pp.G265-G277
- DOI
- 10.1152/ajpgi.00278.2013
- PMID
- 24356880
- PMCID
- PMC3920122
- NLM abbreviation
- Am J Physiol Gastrointest Liver Physiol
- ISSN
- 0193-1857
- eISSN
- 1522-1547
- Publisher
- American Physiological Society; Bethesda, MD
- Language
- English
- Date published
- 02/15/2014
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984047669302771
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