Michele Frison
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frisophagy.bsky.social
Michele Frison
@frisophagy.bsky.social
180 followers 240 following 75 posts
Postdoc in the lab of Patrick Chinnery at the University of Cambridge. Lover of mitophagy and quality control. Fervid European. Obsessive environmentalist. Yoga enthusiast. Way too excited. Curator of mitophagy newsletter - https://biomed.news/bims-tofagi
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frisophagy.bsky.social
Only good papers on mitophagy this week!

biomed.news/bims-tofagi/...

Highlights:
-The bottleneck for maternal transmission of mtDNA is linked to purifying selection by autophagy
-Piecemeal Mitochondrial degradation in plants
-Allophagy?!

Thanks to @biomednews.bsky.social
Altered bottleneck and mitochondrial turnover affect mtDNA mutation load and selection efficiency. (A) Mutational burden was quantified as the total number of mtDNA variants detected per animal. (B) For each animal, the mtDNA N/S ratio was calculated by dividing the number of nonsynonymous variants, normalized to the number of possible nonsynonymous variants in the mitochondrial genome, by the number of synonymous variants, normalized to the number of possible synonymous sites. For (A) and (B): dashed line, median value of the Polg+/+ control group; dotted line, modal value of the Polg+/+ control group; gray, Polg+/+ control group; orange, Polg+/+ Tfam+/− group; blue, Polg+/+ Tfam+/OE group; green, Polg+/+ Bcl2l13−/− group; and pink, Polg+/+ Ulk2−/− group.
November 16, 2025 at 10:53 AM
frisophagy.bsky.social
Mitophagy updates of last week 🪫🗑️

biomed.news/bims-tofagi/...

Highlights:
-two papers on the beneficial effects of mitophagy in CD8+ T cells
-VPS35 mutations in PD affect PINK1/Parkin mitophagy selectively
-review on selective autophagy initiation

Thanks to @biomednews.bsky.social for pre-sorting
Left, soluble SARs such as SQSTM1/p62, NDP52, OPTN, TAX1BP1, and NBR1 are cytosolic proteins that are recruited to cargo on demand. Their recruitment is commonly driven by ubiquitin (Ub) marks on damaged or misfolded cargo, enabling rapid and flexible targeting of diverse substrates. Upon recruitment, these SARs concentrate autophagy initiation factors at the cargo site to initiate autophagosome biogenesis. Right, transmembrane SARs such as NIX, BNIP3, FAM134B, and CCPG1 are stably integrated within organelle membranes. To prevent unwanted autophagy activation, these SARs require additional layers of control. Selective autophagy can be triggered by transcriptional upregulation (e.g., hypoxia-driven induction of NIX/BNIP3), post-translational modifications such as ubiquitination, or SAR clustering. ER-phagy SARs further promote local membrane bending and scission to excise a portion of the organelle for autophagic removal. While some SARs are transcriptionally induced, others—such as FAM134B—are constitutively present and rely primarily on clustering and post-translational regulation, providing SAR-specific modes of control over autophagosome formation.
November 4, 2025 at 5:26 PM
frisophagy.bsky.social
In this week's issue of mitophagy news 🗑️🪫

biomed.news/bims-tofagi/...

-High sugar diet inhbits renal mitophagy and disrupts renal function
-a review by @soleimanpourlab.bsky.social on mitophagy in diabetic ß-cells
-Optineurin is necessary for mitochondrial removal during erythrocyte maturation
Assessment of mitophagy in the Malphigian tubules of the dmt-Keima Drosophila kidney
October 26, 2025 at 8:23 PM
frisophagy.bsky.social
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
October 10, 2025 at 8:45 AM
frisophagy.bsky.social
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
October 10, 2025 at 8:45 AM
frisophagy.bsky.social
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.
October 10, 2025 at 8:45 AM
frisophagy.bsky.social
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
October 10, 2025 at 8:45 AM
frisophagy.bsky.social
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!!
October 10, 2025 at 8:45 AM
frisophagy.bsky.social
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
October 10, 2025 at 8:45 AM
frisophagy.bsky.social
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.
October 5, 2025 at 12:09 PM
frisophagy.bsky.social
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
September 29, 2025 at 8:17 AM
frisophagy.bsky.social
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.
September 14, 2025 at 11:24 AM
frisophagy.bsky.social
In this week's issue of #mitophagy news:

-Mitochondrial damage (AntA) in neurons trigger degradation of negative autophagy regulators
-transcriptional dynamics of mitophagy during muscle development
-And much more 🪫🗑️

Link 👇
biomed.news/bims-tofagi/...
August 17, 2025 at 5:23 PM
frisophagy.bsky.social
Last week's mitophagy news is packed with papers!! 📚🧑‍💻

Full list 👇
biomed.news/bims-tofagi/...

Highlights:
-in vitro reconstitution of receptor-mediated mitophagy reveals key principles
-cytosolic phosphoUbiquitin inhibits proteasomal activity and is neurotoxic

Thanks to @biomednews.bsky.social
Ubiquitin phosphorylation inhibits both ubiquitin chain elongation and ubiquitin proteasome interactions.
August 5, 2025 at 7:23 AM
frisophagy.bsky.social
Below is the link to another week of #mitophagy papers! 🔋🗑️

biomed.news/bims-tofagi/...

Thanks to @biomednews.bsky.social for pre-sorting.

This week's highlight:
PNPLA7 is required for the Parkin-dependent mitophagy shut-down that leads to mitochondrial accumulation in adipose tissue browning
PNPLA7 is a MAM protein and interacts with Parkin to facilitate mitochondrial translocation of Parkin.
July 27, 2025 at 5:18 PM
frisophagy.bsky.social
In this week's mitophagy news🫀🪫🗑️:

-cardiac deficiency in fatty acid oxidation (Cpt2 KO) inhibits cardioprotective mitophagy and is rescued by Usp30 KO
-neuronal metabolism prioritises mitophagy over glycolysis
-Rab7 downregulation impairs cardioprotective mitophagy in ischemic heart failure
July 6, 2025 at 3:18 PM
frisophagy.bsky.social
In this week's #mitophagy news we have novel insights into:

-Parkin's ubiquitination of Miro1🚙
-Swine Fever Virus's induction of mitophagy 🐽🤒
-cardioprotective mitophagy in obesity-associated heart failure🫀🗑️🪫

Papers in the link below
biomed.news/2025-06-29

Thanks to @biomednews.bsky.social
Active Parkin processes ubiquitin most efficiently with Miro1 as substrate
June 29, 2025 at 1:03 PM
frisophagy.bsky.social
Another fantastic week of #mitophagy papers! 🪫🗑️📚

biomed.news/bims-tofagi/...

Highlights:
-astrocyte HK2 interacts with PINK1 to facilitate glucose-rich mitophagy
-Nipsnap1/2 KO accelerates murine ageing
-UBR4 is a mitophagy linked risk factor in lung adenocarcinoma

@biomednews.bsky.social
PINK and Parkin-dependent mitophagy is faster in astrocytes than neurons after mitochondrial depolarization in primary mouse neuronal-glial cultures
June 22, 2025 at 11:26 AM
frisophagy.bsky.social
A short, but exciting report on #mitophagy papers this week!! 🪰🐒

biomed.news/bims-tofagi/...

Thanks to @biomednews.bsky.social

-Mitochondrial fumarate impairs Parkin-dependent mitophagy, but *not* in invertebrates 🪰
-swapping 🚹 mtDNA with 🐒 in iPSCs gives surprising results
June 15, 2025 at 11:39 AM
frisophagy.bsky.social
Fascinating science in this week's #mitophagy news 👁️👁️🔥

biomed.news/bims-tofagi/...

-Retinal development requires a wave of PINK1-dependent mitophagy
-an AI-assisted imaging technique identified a novel mitophagy drug that decreases Abeta aggregation

Thanks to @biomednews.bsky.social
June 8, 2025 at 10:36 AM
frisophagy.bsky.social
Leaving England for my first
#ubiquitin biology conference 🚀🌐📚. So excited for a few days of science 🤩! Mitophagy enthusiasts of all countries, unite! 😆

#WUeBI2025
@grk2243.bsky.social
May 31, 2025 at 7:08 AM
frisophagy.bsky.social
In last week's #mitophagy papers:

-deferiprone as a therapeutic option in photoreceptor degeneration
-alpha-synuclein induces mitophagy by cardiolipin externalisation

Check it out 👇
biomed.news/bims-tofagi/...

All made possible by @biomednews.bsky.social
May 25, 2025 at 1:14 PM
frisophagy.bsky.social
Autophagosome formation at FIB-SEM resolution, as well as tetrahymema mitophagy and models of pulmonary fibrosis, in this week's issue of #mitophagy news. 🪫🗑️

Check it out 👇
biomed.news/bims-tofagi/...
May 19, 2025 at 7:45 AM
frisophagy.bsky.social
Last week's #mitophagy news contains a really diverse mix of papers, with studies on:

-kinome screening of regulators of PINK1 activity
-SNX10 at the crossroads of mitophagy and endocytosis
-structural studies of pharmacological USP30 inhibition

See link below
biomed.news/bims-tofagi/...
Kinome screening for regulators of endogenous PINK1 activity
May 12, 2025 at 3:39 PM
frisophagy.bsky.social
In this week's #mitophagy papers, Rab GTPases take the centre stage, with a systematic study their role in autophagy, showing that multiple "Rabs" selectively mediate the degradation of mitochondria and other cellular components.

Thanks to @biomednews.bsky.social

biomed.news/bims-tofagi/...
Schematic representation of Rab GTPases acting as “eat me” signals for selective autophagy.
April 13, 2025 at 11:29 AM