Lightnews — Scholar-powered news

Michele Frison @frisophagy.bsky.social · 2h

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 · 2h

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

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Michele Frison @frisophagy.bsky.social · 3h

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

Michele Frison @frisophagy.bsky.social · 3h

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

Michele Frison @frisophagy.bsky.social · 3h

Thank you so much 🥳☺️

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Michele Frison @frisophagy.bsky.social · 4h

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.

Michele Frison @frisophagy.bsky.social · 4h

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 · 4h

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 · 4h

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 · 4h

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 · 4h

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 · 4h

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 · 4h

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 · 4h

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 · 4h

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 · 1d

🚨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 · 5d

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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Reposted by Michele Frison

Mongabay @mongabay.com · 7d

Jane Goodall, who revealed the intimate lives of chimpanzees and gave the modern world a language of hope, has died at the age of 91.

“Every individual matters. Every individual has a role to play. Every individual makes a difference,” she told audiences. Those words remain her truest epitaph.

Jane Goodall (1934–2025): primatologist, conservationist, and messenger of hope

Jane Goodall, who revealed the intimate lives of chimpanzees and gave the modern world a language of hope, has died at the age of 91. Over the course of six decades, she moved from an unlikely young…

news.mongabay.com

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Michele Frison @frisophagy.bsky.social · 11d

That's fascinating! So much to learn from comparative studies

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Michele Frison @frisophagy.bsky.social · 11d

Lots of interesting papers in this week's mitophagy news! 🗑️🪫

biomed.news/bims-tofagi/...

-Ubiquitin precursor with C-terminal extension promotes proteostasis and longevity
-Pink1 KO leads to APP-induced dopaminergic pathology
-An OMM-rupture sensor

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Reposted by Michele Frison

Anupam Patgiri @apatgiri.bsky.social · 25d

Replication competition drives the selective mtDNA inheritance in Drosophila ovary www.cell.com/cell-reports...

Replication competition drives the selective mtDNA inheritance in Drosophila ovary

Zhang et al. report a novel imaging method that can distinguish mtDNA variants with single-nucleotide polymorphisms at single-molecule resolution in situ. Using this method, they visualized dynamics o...

www.cell.com

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Michele Frison @frisophagy.bsky.social · 26d

In this week's issue of mitophagy news 🪫🗑️:

-Urolithin A increases healthspan via MERCS and Ca2+-mitophagy
-Parkin Induces Ubiquitination and Large Extracellular Vesicle Release of HMGB1 to Activate Antitumor Immunity
-a Parkin and hTau mouse cross

biomed.news/bims-tofagi/...

Urolithin A ameliorates the age-dependent decline of ER-mitochondria contacts and alters intracellular Ca2+ balance.

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Michele Frison @frisophagy.bsky.social · Sep 8

Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations | Science www.science.org/doi/10.1126/...

Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations

Somatically acquired mitochondrial DNA mutations accumulate with age, but the mechanisms and consequences are poorly understood. Here we show that transient injuries induce a burst of persistent mtDNA...

www.science.org

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Reposted by Michele Frison

Nikita Kozhushko @nikitakozhushko.bsky.social · Sep 8

Celebrating Postdoc Research – National Postdoc Appreciation Week 2025!

#PostdocAppreciationWeek #PostdocResearch #CIMR #MBU #Cambridge #ResearchSeminar #ScienceCommunication #CambridgeUniversity

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Reposted by Michele Frison

The Hassan Brain Development Team @hassanbraindevlab.bsky.social · Sep 1

Latest from the lab, the beautiful work of Iryna Mohylyak and colleagues describing a temporal developmental transcriptional program for mitochondrial quality control and synaptic connectivity, with @jdejuan-sanz.bsky.social, Olga Corti and @steinaerts.bsky.social
labs
www.nature.com/articles/s41...

Temporal transcriptional regulation of mitochondrial morphology primes activity-dependent circuit connectivity - Nature Communications

This study investigates the developmental transcriptional regulation of mitochondrial quality control. Authors identify the Drosophila factor Mirana, homologous to mammalian TZAP, as a key temporal re...

www.nature.com

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