To Mia or not to Mia: stepwise evolution of the mitochondrial intermembrane space disulfide relay

Abstract

The disulfide relay system found in the intermembrane space (IMS) of mitochondria is an essential pathway for the import and oxidative folding of IMS proteins. Erv1, an essential member of this pathway, has been previously found to be ubiquitously present in mitochondria-containing eukaryotes. However, the other essential protein, Mia40, was found to be absent or not required in some organisms, raising questions about how the disulfide relay functions in these organisms. A recent study published in BMC Biology demonstrates for the first time that some Erv1 proteins can function in oxidative folding independently of a Mia40 protein, providing for the first time strong evidence that the IMS disulfide relay evolved in a stepwise manner. See research article: 10.1186/s12915-017-0445-8

The Plant Mitochondrial TAT Pathway Is Essential for Complex III Biogenesis

“…For example, the order of complex I subunit assembly in plants was also demonstrated to be more similar to bacteria, although yeast and mammalian mitochondria have diverged more [44]. The disulfide relay pathway for oxidative folding in the intermembrane space in plants also appears to be an ancient form of the pathway now seen in mammals and yeast [45]. This indicates that there is some constraint on plant mitochondria evolution that makes them more closely resemble bacteria in certain aspects.…”

N-Acetyl-Cysteine: Modulating the Cysteine Redox Proteome in Neurodegenerative Diseases

“…Mia40 has a critical redox-active disulfide bridge in a conserved cysteine-proline-cysteine region that promotes the steady folding of the substrate by introducing disulfide bonds, thus entrapping the substrates within the IMS ( Figure 1 and Figure 2 ). Then, Mia40 is re-oxidized by the ETS translocation variant 1 (Erv1), a protein harboring two fundamental redox-active cysteine-x-x-cysteine pairs that transport the electrons from Mia40 to flavin adenine dinucleotide (FAD) [ 339 , 340 , 341 , 342 ]. To achieve the disulfide interplay, Erv1 is oxidized by cytochrome c that donates the electrons through cytochrome c oxidase to oxygen in the respiratory electron chain [ 342 ].…”

Moschamindole induces glioma cell apoptosis by blocking Mia40‐dependent mitochondrial intermembrane space assembly and oxidative respiration

“…When cytosolic proteins enter the Tom complex channel, which is the main entry gate for transport into the mitochondria, the precursor proteins are specifically recognized by the Mia40 protein, and their cysteine residues are oxidized through the cooperative action of Mia40 and ALR/Erv1. Mia40 functions as a receptor, folding catalyst, and disulphide carrier, and the ALR protein serves as a sulfhydryl oxidase (Carrie & Soll, 2017;Sztolsztener, Brewinska, Guiard, & Chacinska, 2013). After proper folding, Mia40-mediated proteins are translocated across the inner mitochondrial membrane and are destined for the mitochondrial matrix through a translocon formed by Tim23 and Tim17.…”