Oxidative stress and protease dysfunction in the yeast model of Friedreich ataxia

Cells Lacking Pfh1, a Fission Yeast Homolog of Mammalian Frataxin Protein, Display Constitutive Activation of the Iron Starvation Response

“…In particular, yeast frataxin has been suggested to participate in ISC maturation as an iron donor, based on its reported interaction with Isu1 (19,48). However, it has also been demonstrated that restricting oxidative damage, either by decreasing ROS production (49) or by diminishing available iron (50), prevents aconitase inactivation. Furthermore, a conditional knockdown of YFH1 expression has allowed establishing the order of sequential events occurring upon frataxin depletion, indicating that induction of iron import is a primary event leading to the late inactivation of ISC-containing proteins (21).…”

Selective Oma1 Protease-mediated Proteolysis of Cox1 Subunit of Cytochrome Oxidase in Assembly Mutants

“…Assessment of Proteolytic Activity-Proteolytic activity in the mitochondrial membranes was measured following the method adapted from Bulteau et al (30). Mitochondria isolated from various strains were resuspended in hypotonic buffer (20 mM HEPES, pH 7.4) and gently sonicated (3 ϫ 30 s with 50% duty cycle).…”

Loss of Cardiolipin Leads to Perturbation of Mitochondrial and Cellular Iron Homeostasis

“…Defects in mitochondrial Fe-S assembly lead to decreased maturation of both mitochondrial and cytosolic Fe-S proteins (20,28,(31)(32)(33)(34). In addition, excess mitochondrial iron causes oxidative damage to Fe-S clusters due to the formation of reactive oxygen species (ROS) (35)(36)(37).…”