A Disulfide Relay System in the Intermembrane Space of Mitochondria that Mediates Protein Import

SummaryWe describe here a pathway for the import of proteins into the intermembrane space (IMS) of mitochondria. Substrates of this pathway are proteins with conserved cysteine motifs, which are critical for import. After passage through the TOM channel, these proteins are covalently trapped by Mia40 via disulfide bridges. Mia40 contains cysteine residues, which are oxidized by the sulfhydryl oxidase Erv1. Depletion of Erv1 or conditions reducing Mia40 prevent protein import. We propose that Erv1 and Mia40 function as a disulfide relay system that catalyzes the import of proteins into the IMS by an oxidative folding mechanism. The existence of a disulfide exchange system in the IMS is unexpected in view of the free exchange of metabolites between IMS and cytosol via porin channels. We suggest that this process reflects the evolutionary origin of the IMS from the periplasmic space of the prokaryotic ancestors of mitochondria

The disulfide relay system of mitochondria is connected to the respiratory chain

All proteins of the intermembrane space of mitochondria are encoded by nuclear genes and synthesized in the cytosol. Many of these proteins lack presequences but are imported into mitochondria in an oxidation-driven process that relies on the activity of Mia40 and Erv1. Both factors form a disulfide relay system in which Mia40 functions as a receptor that transiently interacts with incoming polypeptides via disulfide bonds. Erv1 is a sulfhydryl oxidase that oxidizes and activates Mia40, but it has remained unclear how Erv1 itself is oxidized. Here, we show that Erv1 passes its electrons on to molecular oxygen via interaction with cytochrome c and cytochrome c oxidase. This connection to the respiratory chain increases the efficient oxidation of the relay system in mitochondria and prevents the formation of toxic hydrogen peroxide. Thus, analogous to the system in the bacterial periplasm, the disulfide relay in the intermembrane space is connected to the electron transport chain of the inner membrane

FLORA, MYCOTA AND VEGETATION OF KUPENA RESERVE (RODOPI MOUNTAINS, BULGARIA)

The paper represents results from recent complex studies of flora, mycota and vegetation within the Kupena Reserve (Rodopi Mts, Bulgaria). Twenty three species, referred to 2 divisions, 4 classes and 16 families are recorded for the bryoflora. The vascular flora is presented by 368 species from 57 families, 121 of which are considered as medicinal plants. Eighty seven species of larger ascomycetes and basidiomycetes are found and reported for first time in the reserve. Four of them are of a high conservation value. The vegetation cover is consisted of mixed and monodominant deciduous and coniferous forests, as well as of mire, riverbank and mesic grasslands. Thirteen types of habitats according to the Habitats Directive classification have been recorded within the reserve

Mia40, a novel factor for protein import into the intermembrane space of mitochondria is able to bind metal ions

AbstractMany proteins located in the intermembrane space (IMS) of mitochondria are characterized by a low molecular mass, contain highly conserved cysteine residues and coordinate metal ions. Studies on one of these proteins, Tim13, revealed that net translocation across the outer membrane is driven by metal-dependent folding in the IMS [1]. We have identified an essential component, Mia40/Tim40/Ykl195w, with a highly conserved domain in the IMS that is able to bind zinc and copper ions. In cells lacking Mia40, the endogenous levels of Tim13 and other metal-binding IMS proteins are strongly reduced due to the impaired import of these proteins. Furthermore, Mia40 directly interacts with newly imported Tim13 protein. We conclude that Mia40 is the first essential component of a specific translocation pathway of metal-binding IMS proteins

Molecular Coverage Determines Sliding Wear Behavior of n-Octadecylphosphonic Acid Functionalized Cu-O Coated Steel Disks against Aluminum

The sliding wear behavior of Cu–O coated steel disks functionalized with n-octadecyl-phosphonic acids was evaluated against aluminum in ball-on-disk tribometer experiments. After 5 m of sliding the friction coefficient of the functionalized sample with maximum molecular coverage is ≤0.3 ± 0.1. Surfaces with lower coverage mitigate friction and wear as well exhibiting initially similar low friction coefficients but reveal the breakdown of lubrication for sliding distances <5 m. The length of the low friction sliding distance before breakdown scales with the coverage of n-octadecylphosphonic acids on the Cu–O surface. Coverage hence determines the tribological behavior of the functionalized surface against sliding aluminum. As the coverage is increased, detrimental asperity contacts between the rubbing surfaces are reduced