Cells Lacking Rieske Iron-Sulfur Protein Have a Reactive Oxygen Species-Associated Decrease in Respiratory Complexes I and IV

Department of Neurology, University of Miami, Miller School of Medicine, Miami, Florida, USA.
Molecular and Cellular Biology (Impact Factor: 4.78). 11/2011; 32(2):415-29. DOI: 10.1128/MCB.06051-11
Source: PubMed


Mitochondrial respiratory complexes of the electron transport chain (CI, CIII, and CIV) can be assembled into larger structures forming supercomplexes. We analyzed the assembly/stability of respiratory complexes in mouse lung fibroblasts lacking the Rieske iron-sulfur protein (RISP knockout [KO]cells), one of the catalytic subunits of CIII. In the absence of RISP, most of the remaining CIII subunits were able to assemble into a large precomplex that lacked enzymatic activity. CI, CIV, and supercomplexes were decreased in the RISP-deficient cells. Reintroduction of RISP into KO cells restored CIII activity and increased the levels of active CI, CIV, and supercomplexes. We found that hypoxia (1% O(2)) resulted in increased levels of CI, CIV, and supercomplex assembly in RISP KO cells. In addition, treatment of control cells with different oxidative phosphorylation (OXPHOS) inhibitors showed that compounds known to generate reactive oxygen species (ROS) (e.g., antimycin A and oligomycin) had a negative impact on CI and supercomplex levels. Accordingly, a superoxide dismutase (SOD) mimetic compound and SOD2 overexpression provided a partial increase in supercomplex levels in the RISP KO cells. Our data suggest that the stability of CI, CIV, and supercomplexes is regulated by ROS in the context of defective oxidative phosphorylation.

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    • "These results suggest an impairment of CI levels/activity induced by the presence of MT-CYB microdeletion, in agreement with several previous reports indicating a tight dependence between CIII mutations and CI assembly/activity [Acin-Perez et al., 2004; Schagger et al., 2004; Blakely et al., 2005]. The reduction of CIV activity observed in both heteroplasmic and homoplasmic cybrids is more difficult to explain and further experiments are needed to shed light on the relationship between MT-CYB mutations and CIV activity that is still controversial and poorly understood [Rana et al., 2000; Acin-Perez et al., 2004; Diaz et al., 2012; Lapuente-Brun et al., 2013]. "
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