How does the cell tune p97/Cdc48 activity for different substrates?
Study suggests different adaptor combinations function as molecular accelerators of protein clearance.
www.science.org/doi/10.1126/...
Last 2 weeks of literature on #Mitochondria in #Health & #Disease! 🤍 💚
biomed.news/bims-mitdis/...
biomed.news/bims-mitdis/...
@biomednews.bsky.social @mitoscientist.bsky.social @gavinmcstay.bsky.social
Vit B2 and B3 nutrigenomics reveals a therapy for NAXD disease
www.cell.com/cell/fulltex...
Join us for a great session @asbmb.bsky.social annual meeting tomorrow. Our session starts at 9:30 am!
❓ Solving mitochondria isolation challenges: Traditional enzymatic methods compromise mitochondrial surface proteins in #Yeast; new glass bead mechanical approach preserves Atg32 integrity for quantitative #Mitophagy analysis
🔬 #YeastResearch #SGD
www.yeastgenome.org/reference/S1...
Super excited to present out work at @mitotalks.bsky.social this Thursday!! Hope to see you there!
New online: Stress adaptation of mitochondrial protein import by OMA1-mediated degradation of DNAJC15
Mitochondrien können offenbar die Zahl der Lipidtröpfchen in der Zelle beeinflussen. Das zeigt eine aktuelle Studie von @unibonn.bsky.social und Universitätsklinikum Bonn sowie der @uni-freiburg.de.
www.nature.com/articles/s41...
🛑 Engineering stop buttons: CRISPR KiSS system in #Yeast conditionally targets essential genes to inhibit growth.
Dual gRNA approach improves performance as researchers continue optimizing for cell factory applications
🧬 #YeastResearch 🧪 #SGD #SyntheticBiology
www.yeastgenome.org/reference/S1...
Ever wondered how the human liver looks like at single-cell, spatial protein resolution? We used single-cell Deep Visual Proteomics to map human liver zonation at the protein level - one hepatocyte at a time. Our paper is out in @natmetabolism.nature.com! www.nature.com/articles/s42...
Really excited to share the first preprint of my postdoc!! A huge thank you to our collaborators, the Niemi Lab powerhouse crew who were incredible helpful, and of course @nieminm.bsky.social who has been an AMAZING mentor through all the unexpected surprises and interesting discoveries we made!
A big day for the lab! Huge congratulations to the newly minted Dr. Jerry Wei @lianjiejerrywei.bsky.social for successfully defending his thesis! 🎓🥳🎉
Finally, I'd like to thank the patients and their families for enrolling in the study, allowing us to find and study these variants. The mitochondrial disease community is inspiring, and many thanks to the United Mitochondrial Disease Foundation for supporting @kerikozul.bsky.social. 12/end
Additionally, we had fantastic support from collaborators Gary Patti and Ben Garcia for metabolomics and proteomics analyses. @kerikozul.bsky.social also recruited tons of help from people in our lab on various analyses, and it was fun to coordinate so many unique contributions! 11/n
A huge shout out to Naif Almontashiri, our collaborator on this project, as well as Ali AlAsmari, the co-lead author with @kerikozul.bsky.social on this work. This was truly a collaborative effort that would not have been possible without both groups. 10/n
Overall, this study has helped to characterize and deorphanize a new gene associated with mitochondrial disease: PPTC7. We hope that this will lead to clearer diagnostics for some patients with mtiochondrial disease, and we are excited to learn more about PPTC7 biology through this lens. 9/n
Interestingly, patients with PPTC7 deficiency show hypomyelinating leukodystrophy - a phenotype not consistently associated with FBXL4 deficiency. This may stem from severe levels of excessive mitophagy, or, possibly, contributions from other PPTC7 functions, such as its phosphatase activity. 8/n
Clinically, PPTC7 deficiency manifests as a severe inborn error of metabolism, with defects in BCAA catabolism, the TCA cycle, the urea cycle, and mirroring some acidurias. Many of these phenotypes are shared with FBXL4 deficiency - a sister mitochondrial disease. 7/n
Remarkably, our co-collaborator Naif Almontashiri was able to find a second family with a homozygous PPTC7 mutation, this time in the 3'UTR. Modeling this mutation in mammalian cells using CRISPR, we were able to demonstrate that this mutation also elevates BNIP3 and NIX-mediated mitophagy. 6/n
This disruption in PPTC7 leads to many of the hallmarks that we had previously found in Pptc7 KO mice and cells, including decreased mitochondrial content, lower mtDNA levels, compromised respiratory capacity, and swollen, fragemented mitochondria. 5/n
She found that the single, homozygous point mutant in PPTC7 identified in the patients, D158N, disrupted not only the ability of PPTC7 to suppress BNIP3-mediated mitophagy, but also its phosphatase activity. 4/n
In early 2024, postdoc extraordinaire @kerikozul.bsky.social joined the lab and took the lead on characterizing the molecular features of the patient mutations in mitochondrial biology and mitophagy. 3/n
In the summer of 2023, we were notified by Genematcher (genematcher.org) that a group had identified homozygous mutations in patients manifesting in severe mitochondrial disease. 2/n
Thrilled to share our latest work "Recessive PPTC7 deficiency triggers excessive mitophagy to cause a severe inborn error of metabolism with hypomyelinating leukodystrophy" - a collaborative effort documenting the first cases of PPTC7 mutations in humans. 1/n
www.researchsquare.com/article/rs-8...
Finally, I'd like to thank the patients and their families in enrolling in the study that allowed us to find these variants. The mitochondrial disease community is inspiring, and many thanks to the United Mitochondrial Disease Foundation for supporting @kerikozul.bsky.social. 12/end
Additionally, we had fantastic support from collaborators Gary Patti and Ben Garcia for metabolomics and proteomics analyses. @kerikozul.bsky.social also recruited tons of help from people in our lab on various analyses, and it was fun to coordinate so many unique contributions! 11/n
A huge shout out to Naif Almontashiri, our collaborator on this project, as well as Ali AlAsmari, the co-lead author with @kerikozul.bsky.social on this work. This was truly a collaborative effort that would not have been possible without both groups. 10/n
Overall, this study has helped to characterize and deorphanize a new gene associated with mitochondrial disease: PPTC7. We hope that this will lead to clearer diagnostics for some patients with mtiochondrial disease, and we are excited to learn more about PPTC7 biology through this lens. 9/n
Interestingly, patients with PPTC7 deficiency all show hypomyelinating leukodystrophy - a phenotype sometimes but not always associated with FBXL4 deficiency. This may stem from either consistently severe levels of excessive mitophagy, or, possibly, contributions from PPTC7 phosphatase activity. 8/n
