Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers

Mitochondria and peroxisomes share a number of common biochemical processes, including the beta oxidation of fatty acids and the scavenging of peroxides. Here, we identify a new outer-membrane mitochondria-anchored protein ligase (MAPL) containing a really interesting new gene (RING)-finger domain. Overexpression of MAPL leads to mitochondrial fragmentation, indicating a regulatory function controlling mitochondrial morphology. In addition, confocal- and electron-microscopy studies of MAPL-YFP led to the observation that MAPL is also incorporated within unique, DRP1-independent, 70-100 nm diameter mitochondria-derived vesicles (MDVs). Importantly, vesicles containing MAPL exclude another outer-membrane marker, TOM20, and vesicles containing TOM20 exclude MAPL, indicating that MDVs selectively incorporate their cargo. We further demonstrate that MAPL-containing vesicles fuse with a subset of peroxisomes, marking the first evidence for a direct relationship between these two functionally related organelles. In contrast, a distinct vesicle population labeled with TOM20 does not fuse with peroxisomes, indicating that the incorporation of specific cargo is a primary determinant of MDV fate. These data are the first to identify MAPL, describe and characterize MDVs, and define a new intracellular transport route between mitochondria and peroxisomes

Av egen kraft tillsammans med andra. Personer med psykiska funktionshinder, socialt stöd och återhämtning

The purpose of this study was to describe and analyse the significance of social support to adults with psychiatric disabilities, based on the individual’s experiences. This includes research questions concerning what type of social support was perceived to be beneficial or restrictive, which relational aspects were considered having a beneficial or restrictive effect on the support- and recovery process, as well as what strategies and capacities the individual developed on their own in order to cope with their obstacles and disadvantages. The empirical material was based on qualitative inteviews with ten individuals that defined themselves as having psychiatric disabilities. They were each interviewed on three occasions. The repetetive form of the interviews lead to three separate interview guides being created over the course of the data collection process. The goal of the first interview was to get a general idea of the subject’s daily life, activities, arenas, relationships and support. The second interview focused on meaningful relationships. The third and final interview had one general and one individual part. The general part focused on the subject’s psychiatric disabilities, their opportunities as well as existing and desired support measures. The subject matters in the individual part were related to the previous interviews with each of the participants and aimed to develop or expand on previous discussion. The material was analysed using theories about social support and recovery and was presented with roots in four different networking entities: close and extended family, friends, coworkers and fellow students, as well as formal support instances. The result showed that it is the support with mobilising qualities that is beneficial to the recovery process. It increases the individual’s degree of control over their illness, obstacles and challenges. In addition, it appeals to the individual as a central actor and as a person with difficulties as well as resources. The fact that the social support from the various support agencies have varying focus and direction benefits recovery since it increases the individual’s opportunity to maintain as well as develop their social bonds and roles within the community. A relational prerequisite for social support is an equal relationship, which benefits the recovery process as it encompasses acknowledgement and acceptance of both the individual on a personal level and of their situation. The type of social support that hinders recovery is the kind that lacks a connection between the individual’s perceived problems, their need for support and their over time fluctuating ability to handle their psychiatric disability. This is due to the fact that it robs the individual of control over the situation, increases the need for support and strengthens their perception of themselves as sick. Recovery comes to a halt when the individual isn’t included in the support and recovery process, which is clarified in relational aspects such as lacking attentiveness, subpar acceptance as well as rejection. The individual’s will and capacity to actively take on the responsibility to steer their recovery in a positive direction was made visible through four groups of strategies that were crystallised through the course of the research; creation of understanding and legitimisation, cultivation, including strategies and the creation of boundaries

Characterization of Signal That Directs C-Tail–anchored Proteins to Mammalian Mitochondrial Outer Membrane

We analyzed the signal that directs the outer membrane protein with the C-terminal transmembrane segment (TMS) to mammalian mitochondria by using yeast Tom5 as a model and green fluorescent protein as a reporter. Deletions or mutations were systematically introduced into the TMS or the flanking regions and their intracellular localization in COS-7 cells was examined using confocal microscopy and cell fractionation. 1) Three basic amino acid residues within the C-terminal five-residue segment (C-segment) contained the information required for mitochondrial-targeting. Reduction of the net positive charge in this segment decreased mitochondrial specificity, and the mutants were distributed throughout the intracellular membranes. 2) Elongation of the TMS interfered with the function of the C-segment and the mutants were delivered to the intracellular membranes. 3) Separation of the TMS and C-segment by linker insertion severely impaired mitochondrial targeting function, leading to mislocalization to the cytoplasm. 4) Mutations or small deletions in the region of the TMS flanking the C-segment also impaired the mitochondrial targeting. Therefore, the moderate length of the TMS, the positive charges in the C-segment, and the distance between or context of the TMS and C-segment are critical for the targeting signal. The structural characteristics of the signal thus defined were also confirmed with mammalian C-tail–anchored protein OMP25