Hoppel 2018 MiPschool Tromso D2

From Bioblast
Jump to: navigation, search
Charles Hoppel
Mitochondrial function during ischemia/reperfusion injury.

Link: MitoEAGLE

Hoppel CL (2018)

Event: MiPschool Tromso-Bergen 2018

COST Action MitoEAGLE

Multiple studies have documented that myocardial ischemia results in progressive damage to the mitochondrial electron transport chain. Oxidative phosphorylation has been used to track the sequence and localize the area of damage. In early ischemia, glutamate oxidation is decreased and appears due to a defect in Complex I, as well as in ATP synthase and the adenine nucleotide translocase. These defects are resolved with reperfusion. Subsequently, a decrease in succinate oxidation occurs with prolonged ischemia suggesting a defect distal to Complex I, which persists with reperfusion. The subsarcolemmal mitochondria (SSmt) located under the sarcolemma are affected earlier in ischemia that those mitochondria between the myofibrils (interfibrillar, IFmt). In rabbit heart with prolonged ischemia, we have identified a defect in cytochrome c oxidase (CIV), a loss of the phospholipid, cardiolipin, as well as of cytochrome c from the SSmt only. Reperfusion did not further damage the mitochondria as these defects persist, but do not progress. Blockade of the electron transfer system with the irreversible inhibitor, rotenone, modulated the ischemic damage with preservation of both cardiolipin and cytochrome c content of the SSmt while improving the oxidation through Complex IV.

In the isolated buffer-perfused rat heart, global ischemia decreases oxidative phosphorylation and damages the distal electron transfer system, with decreased Complex III activity, cytochrome c content, and respiration through Complex IV in both SSmt and IFmt. The defect in Complex III has been identified as a functional loss of the iron-sulfur center of the Rieske iron-sulfur protein (ISP) without loss of the subunit peptide. In the aged rat heart, oxidative function is decreased in the IFmt only with the defect localized to Complex III at Qo site. At the onset of reperfusion in the aged heart, IFmt contain two tandem defect in Complex III, which provides a mechanism for the enhance oxidant production and reperfusion damage. Resolution of the aging Complex II defect in the aged heart resolves the combined defect and the treated-aged heart now behaves like a young heart.


Bioblast editor: Beno M, Plangger M O2k-Network Lab: US OH Cleveland Hoppel CL


Affiliations

Dept Pharmacology Medicine, Case Western Reserve Univ School Medicine, Cleveland, OH, USA

MitoEAGLE recommendations: harmonization of nomenclature

  • Gnaiger 2019 MitoFit Preprint Arch: The general abbreviation for 'mitochondria' or 'mitochondrial' (compare mtDNA) is 'mt'
  • Electron transport chain was converted to Electron transfer system
  • IFM was converted to IFmt
  • SSM was converted to SSmt


Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion  Organism: Rat, Rabbit  Tissue;cell: Heart 

Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 


HRR: Oxygraph-2k  Event: D2, Oral