Structural insights into crista junction formation by the Mic60-Mic19 complex

Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie–shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function

The MINOS complex: Keeper of mitochondrial membrane architecture

Mitochondria are surrounded by two distinct membranes. While the outer membrane confines the organelle, the inner membrane has a key role in cellular energy metabolism. The inner mitochondrial membrane is subdivided into the inner boundary membrane, which is closely opposed to the outer membrane, and large irregular invagi- nations termed cristae. Narrow tubular openings – the crista junctions – connect cristae membrane and inner boundary membrane domains. Additionally, sites of contact between inner boundary and outer mitochondrial membranes are frequently observed. We have recently discovered a mitochondrial inner membrane organizing system (MINOS complex) that is crucial for both, the formation of crista junctions and membrane contact sites. MINOS is composed of six inner membrane proteins: the two highly conserved core subunits Fcj1/mitofilin and Mio10/MINOS1 together with Aim5, Aim13, Aim37 and Mio27. Deletion of FCJ1 or MIO10 in yeast abolishes MINOS formation and leads to a grossly altered mitochondrial ultrastructure with extended stacks of sheet-like cristae membranes and the loss of crista junctions. Moreover, MINOS interacts with several protein complexes of the outer mitochondrial membrane, like the SAM/TOB complex or the TOM complex at membrane contact sites. Formation of MINOS con- tact sites supports the import of precursor proteins from the cytosol into the intermembrane space and outer membrane. A detailed structure/function analysis of Fcj1/mitofilin revealed that membrane tethering, MINOS integrity and formation of crista junctions depend on different Fcj1/mitofilin protein domains

Healthcare seeking behaviours among immigrants in Sweden

Bakgrund: Hälsan i sig och möjligheten att söka vård vid nedsatt hälsa ingår i samhällets folkhälsoansvar. Det ansvaret omfattar även de migranter som finns i Sverige. Hur ohälsa tas omhand inom sjukvården och hur hälsoutvecklingen kan stödjas bland migranter har betydelse för hela samhället och samhällsekonomin. Syfte: Att ta reda på mönstret för migranter när det gäller att söka vård, vad man söker för, vilka hinder som kan finnas för vårdsökande, både bland migranterna själva och i vårdapparaten och hur dessa problem kan överbryggas. Metod: Detta är en litteraturbaserad studie. De metoder och den design som användes för att analysera och granska studierna baseras på STROBE och Malteruds granskningsmal för litteraturer studier samt GRADE för metodstyrkan. Resultat: I den systematiska sökningen identifierades 15 artiklar som uppfyllde sökkriterierna. Dessa användes för att svara på frågorna om vårdsökandet och utgjorde underlag för värderingen av den vetenskapliga styrkan när det gäller fynden relaterade till vårdsökandet. Orsaker till vårdsökande omfattade både infektionssjukdomar och icke smittsamma sjukdomar, bland dessa psykisk ohälsa. Det vårdsökande beteendet är bland annat knutet till kulturella uppfattningen om sjukdomars orsaker men också till språkproblem. Sjukvårdens organisation och personalens attityder utgör också hinder för ett adekvat vårdsökande bland migranter. Slutsats: Vårdsökande beteende hos immigranter i Sverige varierar beroende på bakgrund och etnicitet gällande olika sjukdomar och religiös tro. De mönster som påverkar vårdsökande beteendet är dock desamma hos alla grupper och styrs av kulturella och socioekonomiska faktorer liksom av litteracitet och språkbarriärer.Background: Healthcare seeking behaviours among immigrants in Sweden is a public health issue since the health outcome not only affects immigrants but also the Swedish population, the healthcare system and impacts on the national economy. In order to alleviate the problems and support the development of health among immigrants we need a thorough picture of the situation today. Objectives: To explore the healthcare seeking behaviours of immigrants in Sweden looking at the different epidemiological reasons and challenges faced during healthcare seeking and the support than can be appropriate for combating the challenges. Method: Literature based study. The methods and designs applied in the articles were assessed and graded on method strength by STROBE, Malterud guidelines and GRADE respectively. Result: 15 articles were identified through a systematic search and used to determine the quality and strength of the scientific methods used to explore the questions of the study. Reasons for seeking health care were signs and symptoms, communicable as well as non-communicable diseases, among those mental health issues. Obstacles to seeking health care were cultural background as well as perception of causes of diseases and language barriers; in addition, the organisation of care and the attitudes among providers were also seen as obstacles to seeking healthcare. Conclusion: Health seeking behaviour among immigrants vary according to ethnic backgrounds as pertains to diseases and beliefs. However, the challenges faced are common among the different groups and they range from cultural social economic to health illiteracy and language barriers

Structural insights into crista junction formation by the Mic60-Mic19 complex

Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie-shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function.ISSN:2375-254

Structural insights into crista junction formation by the Mic60-Mic19 complex

Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie-shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function.ISSN:2375-254

Role of mitochondrial inner membrane organizing system in protein biogenesis of the mitochondrial outer membrane

Mitochondria contain two membranes, the outer membrane and the inner membrane with folded cristae. The mitochondrial inner membrane organizing system (MINOS) is a large protein complex required for maintaining inner membrane architecture. MINOS interacts with both preprotein transport machineries of the outer membrane, the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). It is unknown, however, whether MINOS plays a role in the biogenesis of outer membrane proteins. We have dissected the interaction of MINOS with TOM and SAM and report that MINOS binds to both translocases independently. MINOS binds to the SAM complex via the conserved polypeptide transport–associated domain of Sam50. Mitochondria lacking mitofilin, the large core subunit of MINOS, are impaired in the biogenesis of β-barrel proteins of the outer membrane, whereas mutant mitochondria lacking any of the other five MINOS subunits import β-barrel proteins in a manner similar to wild-type mitochondria. We show that mitofilin is required at an early stage of β-barrel biogenesis that includes the initial translocation through the TOM complex. We conclude that MINOS interacts with TOM and SAM independently and that the core subunit mitofilin is involved in biogenesis of outer membrane β-barrel proteins.

Dual Role of Mitofilin in Mitochondrial Membrane Organization and Protein Biogenesis

The mitochondrial inner membrane consists of two domains, inner boundary membrane and cristae membrane that are connected by crista junctions. Mitofilin/Fcj1 was reported to be involved in formation of crista junctions, however, different views exist on its function and possible partner proteins. We report that mitofilin plays a dual role. Mitofilin is part of a large inner membrane complex, and we identify five partner proteins as constituents of the mitochondrial inner membrane organizing system (MINOS) that is required for keeping cristae membranes connected to the inner boundary membrane. Additionally, mitofilin is coupled to the outer membrane and promotes protein import via the mitochondrial intermembrane space assembly pathway. Our findings indicate that mitofilin is a central component of MINOS and functions as a multifunctional regulator of mitochondrial architecture and protein biogenesis.