Kondadi Lab

Substrate-induced assembly and functional mechanism of the bacterial membrane protein insertase SecYEG-YidC 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

Very special feelings to announce this one... A project that started like 10 years ago is reaching the finish line, ready to shine. In a dream-team with @beckmannlab.bsky.social we solved the long-chased structure of the active membrane protein insertase SecYEG-YidC
www.biorxiv.org/content/10.1...

What complex are you if you have a very versatile company in close proximity? The MICOS Complex.
We present the MINDNet: Proximity Proteomics revealing the nanodomain interactome in the mitochondrial inner membrane, done by the talented Yulia and team.

What complex are you if you have a very versatile company in close proximity? The MICOS Complex.
We present the MINDNet: Proximity Proteomics revealing the nanodomain interactome in the mitochondrial inner membrane, done by the talented Yulia and team.

Mitochondria-organelle crosstalk in establishing compartmentalized metabolic homeostasis 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...

Mitochondria-organelle crosstalk in establishing compartmentalized metabolic homeostasis: Molecular Cell www.cell.com/molecular-ce...

Some days are very satisfying as mentor…The Kondadi Lab is thrilled that Rebecca Strohm has won best Poster Prize at the recent Gordon Conference: Mitochondria Metabolism and Signaling at Ventura, California. Congratulations Rebecca💐… Keep going

Dhanendra Tomar on X: "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" / X 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

x.com/dhtomar/stat...
It was great visiting Wake Forest School of Medicine for delivering a talk and discussing great science.

New work from Zaman et al., in the Shutt Lab @mitomorph.bsky.social, describes a novel variant in MFN2 linked to mtDNA-mediated inflammation and muscle myopathy
www.life-science-alliance.org/content/8/6/...

Mitochondria in the Nervous System 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…

Thrilled to announce that the registration for the EMBO workshop „Mitochondria in the Nervous System“ is now open.
Join us from Sep 29th to Oct 2nd in beautiful Engelberg, Switzerland!
meetings.embo.org/event/25-mit...

Have a look at this exciting manuscript!

Today is Rare disease day!
There are over 6000 rare diseases that present with a variety of symptoms affecting all organs. Although we call them rare, they affect over 300 millions of individuals world-wide. Help raise awareness, so we, scientists, can search for cures.

Congratulations Oleh 👏

Compositionally unique mitochondria in filopodia support cellular migration 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...

Some good news (and fresh science) to break things up! Our work identifying a subpopulation of compositionally unique mitochondria that localize to filopodia and promote cell migration is now @currentbiology.bsky.social! Led by fantastic @madeleinempavey.bsky.social!

www.cell.com/current-biol...

Dual regulation of mitochondrial fusion by Parkin–PINK1 and OMA1 - Nature 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, ...

www.nature.com/articles/s41...

Well done HaGe and Company 👏

One enzyme, two mechanisms: A team led by @haukehillen.bsky.social from our institute and the University Medical Center Göttingen has uncovered how the 3’ ends of tRNAs are trimmed in the nucleus and mitochondria. ⬇️
www.mpinat.mpg.de/4919943/m_2503

Congratulations Christoph, Simon and the whole team 👏

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

Researchers discovered that long-term #intermittentfasting might be unsafe for teenagers, as it can disrupt the development of #insulin-producing #betacells and potentially raise the risk of #metabolicdisorders: go.tum.de/160744

@www.helmholtz-munich.de @barteltlab.bsky.social

📷L.Matta

Protein codes promote selective subcellular compartmentalization 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 ...

www.science.org/doi/10.1126/...

Lactate homeostasis is maintained through regulation of glycolysis and lipolysis 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...

Lactate homeostasis is maintained through regulation of glycolysis and lipolysis: Cell Metabolism www.cell.com/cell-metabol...

Nice one Alessandro 👏

Good one Alexis And Team 💐

Recommendations for mitochondria transfer and transplantation nomenclature and characterization - Nature Metabolism This Consensus Statement provides a nomenclature framework and experimental recommendations for studying mitochondrial transfer and transplantation.

You've heard of organ transplants, but what about mitochondria transplantation? I joined Jon Brestoff to co-lead 31 scientists from 13 countries to chart the future of this emerging field, which is now published in Nature Metabolism.

www.nature.com/articles/s42...

Triacylglycerol mobilization underpins mitochondrial stress recovery - Nature Cell Biology Baker et al. show that mitochondrial stress recovery requires mobilization of lipid droplet triacylglycerol stores to facilitate cardiolipin biosynthesis and mitochondrial biogenesis.

www.nature.com/articles/s41...

How and when to measure mitochondrial inner membrane potentials 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.

Mitochondria vibes only! Want to measure the inner membrane potential but unsure how or when? This review breaks it down! From protocols to pitfalls, get the tools you need to decode cellular powerhouses. ow.ly/Ejj050UsK7Y

Please add us @cohenlaboratory.bsky.social . Thank You!

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency 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...

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency www.biorxiv.org/content/10.1...

Last days to apply for working with us
👇

Merry Cristae-Mas
Mitochondria are among nature's most remarkable gifts to us. These tiny powerhouses are essential for energy metabolism and stand at the forefront of anti-aging science, serving as the driving force behind strategies to promote healthy longevity.

New: @themitotracker.bsky.social et al. from @labfriedman.bsky.social identify a mitochondrial inner membrane protein that marks and facilitates a subset of sites of mitochondrial fission in human cells. rupress.org/jcb/article/...