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Reposted by Michele Frison

Jack Collier @mitocollier.bsky.social · 1d

🔥 Check out our new paper! @natcellbio.nature.com
Also thanks to @embo.org for their Postdoctoral Fellowship and especially to Mai and Heidi, I learned more than I could ever have imagined in Montreal 🇨🇦 🍁

Heidi M McBride @mitodynamics.bsky.social · 1d

New paper - MAPL strikes again! Interested in mitochondrial signalling, inflammation, lysosome biology, pyroptosis, and Parkinson's disease? Have a look, there's something for everyone! Feeling grateful! @mitocollier.bsky.social Funded by #CIHR, @asapresearch.parkinsonsroadmap.org.
rdcu.be/eKKz1 🇨🇦

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Reposted by Michele Frison

Euromit-2026 @euromit-2026.bsky.social · 1d

📢 Check out this exciting new study by Professor Patrick Chinnery from @mrc-mbu.bsky.social, who will be joining #Euromit2026 as keynote speaker!

pubmed.ncbi.nlm.nih.gov/41066576/

#MitochondrialDisease #mtDNA #mitochondria #euromit2026
@ua-recherche.bsky.social @chuangers.bsky.social

Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations - PubMed

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

pubmed.ncbi.nlm.nih.gov

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Michele Frison @frisophagy.bsky.social · 3d

Thank you so much 🥹 🗑️🪫❤️🥚

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Michele Frison @frisophagy.bsky.social · 4d

Thank you so much Cory! Keeping a look out for more great science from your side

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Reposted by Michele Frison

Johannes Zuber @johanneszuber.bsky.social · 6d

Just out in @science.org: Together with the lab of @wilhelmpalm.bsky.social, we used sequential in-vitro/in-vivo CRISPR screens to decipher metabolic adaptations in tumors. We find that acidosis is a dominant factor that shapes energy metabolism and stress resilience. www.science.org/doi/10.1126/...

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Michele Frison @frisophagy.bsky.social · 5d

Thank you so much Alessandro! Hopefully see you again sometime soon!

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Michele Frison @frisophagy.bsky.social · 5d

Thank you Alex, for your help throughout this project and your ubiquitin and mitophagy wisdom! I was really luck to end up working in the same institute as your lab

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Michele Frison @frisophagy.bsky.social · 5d

Thank you so much Elias!! The situation in vivo is quite complex, but there's evidence for a role of receptor-mediated mitophagy in germline purifying selection. We still don't know though, if it's two parts of the same mechanisms, or two consecutive QC phenomena

journals.plos.org/plosgenetics...

A role for BCL2L13 and autophagy in germline purifying selection of mtDNA

Author summary We have addressed the role of autophagy on purifying selection of mtDNA by mating different autophagy-deficient mouse models, including knockouts of Parkin, Bcl2l13, Ulk1, and Ulk2, to ...

journals.plos.org

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Michele Frison @frisophagy.bsky.social · 5d

Thank you so much Viktor :) Thank god you published your paper on NAD+, autophagy and cell death! The choice of galactose in Figure 4 is all thanks to your lab!! And seeing that the survival experiments followed what you observed was such an important sanity check

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Michele Frison @frisophagy.bsky.social · 5d

Thank youuu 😍😍 This would have been nothing without your Western blotting teachings

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Michele Frison @frisophagy.bsky.social · 5d

Thank you so much Dylan🤸 without your encouragement and wishes it would have taken even longer 🤣🤣

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Michele Frison @frisophagy.bsky.social · 5d

Thank you so much @soleimanpourlab.bsky.social! It's a pleasure to contribute to the community

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Michele Frison @frisophagy.bsky.social · 5d

Thank you so much 🥳☺️

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Michele Frison @frisophagy.bsky.social · 5d

And cannot forget the mention Lisa, Luisca and Julien from @prudentlab.bsky.social b.bsky.social, who gave me lots of advice throughout the process.

And same to @labwhitworth.bsky.social! Your ubiquitin expertise was essential in making this happen.

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Michele Frison @frisophagy.bsky.social · 5d

Last, but not least, I would like to thank all the members of @mitocamb.bsky.social and of the Chinnery lab, without whom none of this would have been possible. This is a fantastic place to work!!

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Michele Frison @frisophagy.bsky.social · 5d

Importantly, we were able to replicate our finding in vitro using not one, but two different systems to inhibit USP30. One of them shows the viability of a therapeutic strategy using small molecule USP30 inhibitors for heteroplasmic mitochondrial disease, which affects 1:8000 people

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Michele Frison @frisophagy.bsky.social · 5d

But this is also a very exciting finding for #mitophagy! When a sperm fertilises an oocyte, a wave of autophagy is activated, but increasing mitochondrial ubiquitination can boost mitophagic quality control and remove mutant mtDNA.

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

Autophagy Is Essential for Preimplantation Development of Mouse Embryos

After fertilization, maternal proteins in oocytes are degraded and new proteins encoded by the zygotic genome are synthesized. We found that autophagy, a process for the degradation of cytoplasmic con...

www.science.org

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Michele Frison @frisophagy.bsky.social · 5d

By comparing the Usp30-mediated heteroplasmy shift from mother to offspring between different types of crosses, we were also able to extrapolate the exact timing of selection, the maternal zygotic transition!! This is an ideal timing for clinical treatment, exploitable during In Vitro Fertilisation

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Michele Frison @frisophagy.bsky.social · 5d

Therefore, restoring mitochondrial ubiquitination by constitutively knocking out Usp30 decreases heteroplasmy from mother to offspring. This process is extremely important for mitochondrial disease patients carrying heteroplasmic mutations, around 1:8000 people.

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Michele Frison @frisophagy.bsky.social · 5d

Interestingly, we found that the mutation does not decrease levels of specific mitophagy protein (e.g. Parkin or PINK1), but rather, mildly, decreases the expression of the proteasome and of many E2 ligases and a few E3s, never previously linked to mitophagy

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Michele Frison @frisophagy.bsky.social · 5d

The impairment of mitophagy is a survival mechanism for the mutation, allowing it to unspecifically increase the total amount of mtDNA and restore absolute copies of WT mtDNA, even at high heteroplasmies!!

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Michele Frison @frisophagy.bsky.social · 5d

Bluesky, I am pleased to present to you the main product of postdoc work, published in @science.org ☝️

As it turns out, the very quality control mechanism that can remove mutant mtDNA copies is the one that maintains high mutant burden, or heteroplasmy levels

High heteroplasmy decreases mitochondrial ubiquitination

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Michele Frison @frisophagy.bsky.social · 5d

How can mitophagy be an effective quality control mechanism if mtDNA mutations reach high enough levels to cause disease?

This question led us into a dark path, full of concepts of evolutionary genetics, germline stem cell biology and mito-nuclear compatibility.

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

Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

www.science.org

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Reposted by Michele Frison

Scott Soleimanpour @soleimanpourlab.bsky.social · 7d

🚨How do mitochondria sense and respond to metabolic stress from the environment in diabetes? 🤔

In new work out in #ScienceAdvances, we show that innate immune signaling promotes β cell compensation for metabolic stress by engaging mitophagy. 🚨1/n
www.science.org/doi/10.1126/...

TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and Parkin-independent mitophagy

TRAF6 bridges innate immune signaling to mitophagy to promote glucose control during metabolic stress.

www.science.org

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Michele Frison @frisophagy.bsky.social · 10d

In this week's mitophagy news 🪫🗑️

biomed.news/bims-tofagi/...

⚡The PP2A-B55α phosphatase is a master regulator of mitochondrial degradation and biogenesis⚡
-Mitochondrial ROS triggers mitophagy through activating the DNA damage response signaling pathway

Thanks to @biomednews.bsky.social

PP2A-B55α activates TFEB upon mitochondrial damage to support Parkin-dependent mitophagy.

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