Estrogen-related receptor α (ERRα) : a novel target in type 2 diabetes

Recent studies have shown that reduced mitochondrial content and function in skeletal muscle are common features of type 2 diabetes. Here, we review the molecular mechanisms involved in the regulation of mitochondrial genes in skeletal muscle, focusing on a key transcriptional network consisting of ERRα and PGC-1α. We describe how knowledge of this transcriptional circuit can be translated to the development of novel therapies for type 2 diabetes

Functional Genomic Analysis of Human Mitochondrial RNA Processing

SummaryBoth strands of human mtDNA are transcribed in continuous, multigenic units that are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory chain biogenesis. We sought to systematically identify nuclear-encoded proteins that contribute to processing of mtRNAs within the organelle. First, we devised and validated a multiplex MitoString assay that quantitates 27 mature and precursor mtDNA transcripts. Second, we applied MitoString profiling to evaluate the impact of silencing each of 107 mitochondrial-localized, predicted RNA-binding proteins. With the resulting data set, we rediscovered the roles of recently identified RNA-processing enzymes, detected unanticipated roles of known disease genes in RNA processing, and identified new regulatory factors. We demonstrate that one such factor, FASTKD4, modulates the half-lives of a subset of mt-mRNAs and associates with mtRNAs in vivo. MitoString profiling may be useful for diagnosing and deciphering the pathogenesis of mtDNA disorders

Cryo-EM structure of a fungal mitochondrial calcium uniporter.

The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel localized to the inner mitochondrial membrane. Here, we describe the structure of an MCU orthologue from the fungus Neosartorya fischeri (NfMCU) determined to 3.8 Å resolution by phase-plate cryo-electron microscopy. The channel is a homotetramer with two-fold symmetry in its amino-terminal domain (NTD) that adopts a similar structure to that of human MCU. The NTD assembles as a dimer of dimers to form a tetrameric ring that connects to the transmembrane domain through an elongated coiled-coil domain. The ion-conducting pore domain maintains four-fold symmetry, with the selectivity filter positioned at the start of the pore-forming TM2 helix. The aspartate and glutamate sidechains of the conserved DIME motif are oriented towards the central axis and separated by one helical turn. The structure of NfMCU offers insights into channel assembly, selective calcium permeation, and inhibitor binding

Tuberculosis of symphysis pubis in a 17 year old male: a rare case presentation and review of literature

Tuberculosis of symphysis pubis is a rare condition with hardly any report of such cases in the last decade. It is necessary to distinguish the entity from more common ones like Osteitis pubis and Osteomyelitis of pubis symphysis by urgent means in order to start the treatment early and thereby minimize morbidity and prevent complications. A rare case of tuberculosis of symphysis pubis in a 17 year old male is described. A high index of suspicion along with an extensive workup including 3-phase bone scan and fine needle aspiration led to the diagnosis. The patient had an excellent outcome following a complete course of multidrug chemotherapy for tuberculosis

MCU encodes the pore conducting mitochondrial calcium currents

Mitochondrial calcium (Ca2+) import is a well-described phenomenon regulating cell survival and ATP production. Of multiple pathways allowing such entry, the mitochondrial Ca2+ uniporter is a highly Ca2+-selective channel complex encoded by several recently-discovered genes. However, the identity of the pore-forming subunit remains to be established, since knockdown of all the candidate uniporter genes inhibit Ca2+ uptake in imaging assays, and reconstitution experiments have been equivocal. To definitively identify the channel, we use whole-mitoplast voltage-clamping, the technique that originally established the uniporter as a Ca2+ channel. We show that RNAi-mediated knockdown of the mitochondrial calcium uniporter (MCU) gene reduces mitochondrial Ca2+ current (IMiCa), whereas overexpression increases it. Additionally, a classic feature of IMiCa, its sensitivity to ruthenium red inhibition, can be abolished by a point mutation in the putative pore domain without altering current magnitude. These analyses establish that MCU encodes the pore-forming subunit of the uniporter channel. DOI: http://dx.doi.org/10.7554/eLife.00704.00