Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase

The biogenesis of mitochondrial intermembrane space proteins depends on specific machinery that transfers disulfide bonds to precursor proteins. The machinery shares features with protein relays for disulfide bond formation in the bacterial periplasm and endoplasmic reticulum. A disulfide-generating enzyme/sulfhydryl oxidase oxidizes a disulfide carrier protein, which in turn transfers a disulfide to the substrate protein. Current views suggest that the disulfide carrier alternates between binding to the oxidase and the substrate. We have analyzed the cooperation of the disulfide relay components during import of precursors into mitochondria and identified a ternary complex of all three components. The ternary complex represents a transient and intermediate step in the oxidation of intermembrane space precursors, where the oxidase Erv1 promotes disulfide transfer to the precursor while both oxidase and precursor are associated with the disulfide carrier Mia40

Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability

The TIM22 complex mediates the import of hydrophobic carrier proteins into the mitochondrial inner membrane. While the TIM22 machinery has been well characterised in yeast, the human complex remains poorly characterised. Here, we identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it’s C-terminus exposed to the intermembrane space. Tim29 is required for the stability of the TIM22 complex and functions in the assembly of hTim22. Furthermore, Tim29 contacts the Translocase of the Outer Mitochondrial Membrane, TOM complex, enabling a mechanism for transport of hydrophobic carrier substrates across the aqueous intermembrane space. Identification of Tim29 highlights the significance of analysing mitochondrial import systems across phylogenetic boundaries, which can reveal novel components and mechanisms in higher organisms

Two decades of forest-related legislation changes in European countries analysed from a property rights perspective

In the last two decades, attention on forests and ownership rights has increased in different domains of international policy, particularly in relation to achieving the global sustainable development goals. This paper looks at the changes in forest-specific legislation applicable to regular productive forests, across 28 European countries. We compare the legal framework applicable in the mid-1990s with that applicable in 2015, using the Property Rights Index in Forestry (PRIF) to measure changes across time and space. The paper shows that forest owners in most western European countries already had high decision-making power in the mid-1990s, following deregulation trends from the 1980s; and for the next two decades, distribution of rights remained largely stable. For these countries, the content and direction of changes indicate that the main pressure on forest-focused legislation comes from environmental discourses (e.g. biodiversity and climate change policies). In contrast, former socialist countries in the mid-1990s gave lower decision-making powers to forest owners than in any of the Western Europe countries; over the next 20 years these show remarkable changes in management, exclusion and withdrawal rights. As a result of these changes, there is no longer a clear line between western and former socialist countries with respect to the national governance systems used to address private forest ownership. Nevertheless, with the exception of Baltic countries which have moved towards the western forest governance system, most of the former socialist countries still maintain a state-centred approach in private forest management. Overall, most of the changes we identified in the last two decades across Europe were recorded in the categories of management rights and exclusion rights. These changes reflect the general trend in European forest policies to expand and reinforce the landowners' individual rights, while preserving minimal rights for other categories of forest users; and to promote the use of financial instruments when targeting policy goals related to the environmental discourse

Mitochondrial biology and dysfunction in secondary mitochondrial disease

Mitochondrial diseases are a broad, genetically heterogeneous class of metabolic disorders characterized by deficits in oxidative phosphorylation (OXPHOS). Primary mitochondrial disease (PMD) defines pathologies resulting from mutation of mitochondrial DNA (mtDNA) or nuclear genes affecting either mtDNA expression or the biogenesis and function of the respiratory chain. Secondary mitochondrial disease (SMD) arises due to mutation of nuclear-encoded genes independent of, or indirectly influencing OXPHOS assembly and operation. Despite instances of novel SMD increasing year-on-year, PMD is much more widely discussed in the literature. Indeed, since the implementation of next generation sequencing (NGS) techniques in 2010, many novel mitochondrial disease genes have been identified, approximately half of which are linked to SMD. This review will consolidate existing knowledge of SMDs and outline discrete categories within which to better understand the diversity of SMD phenotypes. By providing context to the biochemical and molecular pathways perturbed in SMD, we hope to further demonstrate the intricacies of SMD pathologies outside of their indirect contribution to mitochondrial energy generation