2018年4月20日 · Here we describe a mechanism by which Mfn2, a mitochondria-ER tether, gates the autophagic turnover of mitochondria by PINK1 and parkin. Mitochondria-ER appositions are destroyed during mitophagy, and reducing mitochondria-ER contacts increases the rate of mitochondrial degradation.

2022年1月19日 · Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin (pUb) in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via pUb at these sites.

2018年8月21日 · We found that ubiquitination of MFN2 by PRKN occurs rapidly at the onset of mitophagy compared to other PRKN substrates on the OMM, an effect that we are able to recapitulate in a cell-free mitochondrial ubiquitination (‘in organello’) assay involving purified mitochondria, recombinant PRKN and Ub assay components. Indeed, we found that ...

2025年2月10日 · Here we identify a role of MFN2 in quality control independent of its function in organellar shape remodeling. MFN2 ablation alters the cellular proteome, marked for example by decreased levels...

2013年7月11日 · We report here that MITOL regulates mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) domain formation through mitofusin2 (Mfn2). MITOL interacts with and ubiquitinates mitochondrial Mfn2, but not ER-associated Mfn2. Mutation analysis identified a specific interaction between MITOL C-terminal domain and Mfn2 HR1 domain.

2011年3月8日 · Mfn2 – mitofusin 2; Ub-Mfn2 – ubiquitinated mitofusin 2. To determine the subcellular localization of ubiquitinated Mfn1 and 2 in control fibroblasts, cells were incubated with 1 µM valinomycin for 6 h and mitochondrial and cytosolic protein fractions separated.

2020年8月25日 · Mitofusin 2 (Mfn2) plays a major role in mitochondrial fusion and in the maintenance of mitochondria-endoplasmic reticulum contact sites. Given that macrophages play a major role in inflammation, we studied the contribution of Mfn2 to the activity of these cells.

2018年12月1日 · Mitochondrial pro-fusion protein Mitofusins (Mfn1 and Mfn2) were found to be a target for Parkin mediated ubiquitination. Mfns are transmembrane GTPase embedded in the outer membrane of mitochondria, which are required on adjacent mitochondria to mediate fusion.

Mitofusin-2 (Mfn2) is a highly conserved transmembrane GTPase which plays a critical role in mitochondrial fusion process. Recent data have been demonstrated that Mfn2 is involved in the regulation of several crucial cellular pathways beyond fusion, including mitochondrial metabolism, cellular signaling cascade, apoptosis and proliferation.

2012年8月24日 · In this study we examine the relationship between Mfn2 and stress-induced apoptosis. We establish that Mfn2 is a substrate for Jun N-terminal kinase (JNK), which becomes activated in response to genotoxic stresses including doxorubicin (DR; Adriamycin) as well as other cellular stresses.