Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNAAla mutation (m.5019A>G) in mice and demonstrate that macrophages...

organized by Arun Kumar Kondadi and Andreas Reichert

The universally conserved Sec translocon and the YidC/Oxa1-type insertases mediate biogenesis of alpha-helical membrane proteins, but the molecular basis of their cooperation has remained disputed over decades. A recent discovery of a multi-subunit insertase in eukaryotes has raised the question about the architecture of the putative bacterial ortholog SecYEG-YidC and its functional mechanism. Here, we combine cryogenic electron microscopy with cell-free protein synthesis in nanodiscs to visualize biogenesis of the polytopic membrane protein NuoK, the subunit K of NADH-quinone oxidoreductase, that requires both SecYEG and YidC for insertion. We demonstrate that YidC is recruited to the back of the translocon at the late stage of the substrate insertion, in resemblance to the eukaryotic system, and in vivo experiments indicate that the complex assembly is vital for the cells. The nascent chain does not utilize the lateral gate of SecYEG, but enters the lipid membrane at the SecYE-YidC interface, with YidC being the primary insertase. SecYEG-YidC complex promotes folding of the nascent helices at the interface prior their insertion, so the examined cellular pathway follows the fundamental thermodynamic principles of membrane protein folding. Our data provide the first detailed insight on the elusive insertase machinery in the physiologically relevant environment, highlight the importance of the nascent chain for its assembly, and prove the evolutionary conservation of the gate-independent insertion route. ### Competing Interest Statement The authors have declared no competing interest. Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, Ke1879/3, 267205415 (CRC 1208) European Research Council, https://ror.org/0472cxd90, CRYOTRANSLATION

Mitochondria are metabolic hubs that communicate with other organelles via metabolite-, lipid-, and signaling-molecule exchange facilitated by membrane contact sites (MCSs). MCSs, regulated by tetheri...

It was a pleasure hosting our friends and collaborators from across the pond! @AnandMito_Lab & @KondadiLab shared fascinating insights into mitochondrial architecture and dynamics @wakeforestmed #Mitochondria #RedoxBiology #Science https://t.co/n2ia2S1Agu

The brain is a high energy-demanding tissue with an heterogenous cellular composition. Most of the energy consumed is used for maintenance of neuronal synaptic transmission, and neurons almost exclus…

Marlar-Pavey et al. determine that a subpopulation of compositionally unique mitochondria, METEORs, dynamically localize to filopodia. Loss of mitochondrial targeting to filopodia correlates with a re...

We find that, in mice, although the individual loss of Parkin or OMA1 does not affect mitochondrial integrity, their combined loss results in small body size, low locomotor activity, premature death, ...

Long-term intermittent fasting in adolescents may disrupt the development of beta cells, which are important for insulin production.

Cells have evolved mechanisms to distribute ~10 billion protein molecules to subcellular compartments where diverse proteins involved in shared functions must assemble. Here, we demonstrate that proteins with shared functions share amino acid sequence ...

Lactate elevations are a hallmark of human disease, but the mechanisms regulating lactate levels remain poorly understood. Here, Lee et al. elucidate the mechanisms of lactate homeostasis. These invol...