Using single-cell tissue imaging and spatial proteomics to study mitochondria–lipid droplet coupling in hepatocytes, PLIN5 phosphorylation is identified as a mediator of lipid flux and nutrient stress...

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...

This Consensus Statement provides a nomenclature framework and experimental recommendations for studying mitochondrial transfer and transplantation.

Baker et al. show that mitochondrial stress recovery requires mobilization of lipid droplet triacylglycerol stores to facilitate cardiolipin biosynthesis and mitochondrial biogenesis.

The scientific literature on mitochondria has increased significantly over the years due to findings that these organelles have widespread roles in the onset and progression of pathological conditions such as metabolic disorders, neurodegenerative and cardiovascular diseases, inflammation, and cancer. Researchers have extensively explored how mitochondrial properties and functions are modified in different models, often using fluorescent inner mitochondrial membrane potential (ΔΨm) probes to assess functional mitochondrial aspects such as protonmotive force and oxidative phosphorylation.

Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD...

Nuclear DNA damage activates fatty acid–fueled mitochondrial energy metabolism to induce cellular senescence, a hallmark of aging.

Better support structures would “lead to a more inclusive, productive, and humane workplace for everyone,” this physician-scientist writes

Huang et al. conducted a comprehensive review of the literature on metabolomic aging clocks. They particularly emphasized how metabolomic aging clocks, as a novel tool for quantifying aging, are developed, applied, and interpreted.

This work identifies reactive oxygen species released by the electron transport chain as sentinel molecules that regulate localized protein degradation at mitochondrial TOM complexes, a mechanism that controls mitochondrial protein import and adjusts the abundance of the electron transport chain to cellular needs.