Michele Frison

@frisophagy.bsky.social

217 Followers 247 Following

Junior Group Leader at Goethe University Frankfurt. Lover of mitophagy and quality control. Fervid European. Obsessive environmentalist. Yoga enthusiast. Way too excited. Curator of mitophagy newsletter - https://biomed.news/bims-tofagi

Figure 1. Rab1A and Rab1B MitoID ident ifies novel Rab1 effectors. (A) Schematic of the Rab1-MitoID approach in which Rab1 is fused to the promiscuous biotin ligase BirA* and a mitochondrial localization signal from monoamine oxidase (depicted in red), resulting in the relocalization of Rab1 to the mitochondrial membrane. Rab1 interactors will be efficiently biotinylated, while other Golgi proteins and Rab interactors are not. (B) Two-dimensional plot comparing the enrichment of proteins biotinylated by Rab1A-MitoID vs control (BirA alone), plotted against the enrichment of proteins biotinylated with GTP-locked Rab1A (QL) vs GDP-locked Rab1A (SN). For the x axis, the value plotted is that for the nucleotide form of Rab1 that gave the greatest fold change over background. For clarity, Rab1A itself is not shown, as it is part of the BirA* construct. Known effectors and regulators are indicated, with known effectors being enriched in the upper right quadrant. Zoomed regions to the right show a region demarcated by well-enriched known effectors with novel proteins of note identified. For all protein identities and enrichment values see Table S1. (C) as for (B) except with Rab1B rather than Rab1A. (D) Overrepresented GO terms for biological process of the proteins within the regions demarcated by known effectors shown in B and C with the known effectors removed. Ranking is by the summed FDR and enrichment rank. (E) Immunoblots of binding to GST-Rab1A–coated beads of the indicated proteins from HEK293A cell lysates. Rab1A was either Q70L (GTP) or S25N (GDP). The known Rab1 effector RABEP1 (rabaptin-5) is included as positive control (Valsdottir et al., 2001). Source data are available for this figure: SourceData F1.
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.
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.
Assessment of mitophagy in the Malphigian tubules of the dmt-Keima Drosophila kidney
High heteroplasmy decreases mitochondrial ubiquitination
PP2A-B55α activates TFEB upon mitochondrial damage to support Parkin-dependent mitophagy.
Urolithin A ameliorates the age-dependent decline of ER-mitochondria contacts and alters intracellular Ca2+ balance.
Ubiquitin phosphorylation inhibits both ubiquitin chain elongation and ubiquitin proteasome interactions.
PNPLA7 is a MAM protein and interacts with Parkin to facilitate mitochondrial translocation of Parkin.
Active Parkin processes ubiquitin most efficiently with Miro1 as substrate
PINK and Parkin-dependent mitophagy is faster in astrocytes than neurons after mitochondrial depolarization in primary mouse neuronal-glial cultures
DRP1KO HeLa cells expressing mito-mCherry and GFP-LC3 were treated with DFP for 16 h and processed for CLEM-FIB–scanning EM
Kinome screening for regulators of endogenous PINK1 activity
Schematic representation of Rab GTPases acting as “eat me” signals for selective autophagy.
Advances in mitophagy initiation mechanisms
The clearance mechanism of mitochondrial nucleoids upon stress stimulation of mitochondria