Disruption of cytochrome c heme coordination is responsible for mitochondrial injury during ischemia.

ABSTRACT:

Background

It was recently suggested that electron flow into cyt c, coupled with ROS generation, oxidizes cyt c Met(80) to Met(80) sulfoxide (Met-O) in isolated hearts after ischemia-reperfusion, and converts cyt c to a peroxidase. We hypothesize that ischemia disrupts Met(80)-Fe ligation of cyt c, forming pentacoordinated heme Fe(2+), which inhibits electron transport (ET) and promotes oxygenase activity.

Methods

SS-20 (Phe-D-Arg-Phe-Lys-NH2) was used to demonstrate the role of Met(80)-Fe ligation in ischemia. Mitochondria were isolated from ischemic rat kidneys to determine sites of respiratory inhibition. Mitochondrial cyt c and cyt c Met-O were quantified by western blot, and cristae architecture was examined by electron microscopy.

Results

Biochemical and structu

SUBMITTER: Birk AV 

PROVIDER: S-EPMC4547887 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature