The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy
Open accessAbstract
Despite their importance as signaling hubs, the function of mitochondria-ER contact sites in mitochondrial quality control pathways remains unexplored. 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. Mechanistically, parkin/PINK1 catalyze a rapid burst of Mfn2 phosphoubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane, dissociating mitochondria from the ER. We additionally demonstrate that a major portion of the facilitatory effect of p97 on mitophagy is epistatic to Mfn2 and promotes the availability of other parkin substrates such as VDAC1. Finally, we reconstitute the action of these factors on Mfn2 and VDAC1 ubiquitination in a cell-free assay. We show that mitochondria-ER tethering suppresses mitophagy and describe a parkin-/PINK1-dependent mechanism that regulates the destruction of mitochondria-ER contact sites.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
Lazarou, M., Sliter, D. A., Kane, L. A., Sarraf, S. A., Wang, C., Burman, J. L., Sideris, D. P., Fogel, A. I., & Youle, R. J. (2015) · Nature · doi:10.1038/nature14893 · Cited by 2,774
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
de Brito, O. M., & Scorrano, L. (2008) · Nature · doi:10.1038/nature07534 · Cited by 2,442
Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
Tanaka, A., Cleland, M. M., Xu, S., Narendra, D. P., Suen, D.-F., Karbowski, M., & Youle, R. J. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201007013 · Cited by 1,369 · cited 7×
“…of ubiquitinated Mfn1 and Mfn2 with GFP-parkinWT at one hour CCCP (corresponding to the Ub burst observed in Figure 2B), with no apparent binding at four hours (Figure 2C), likely due to turnover of the Mfns by the proteasome at this time (Figures 1G and 2B and [Tanaka et al., 2010]).”
BackgroundResultInfluentialA new pathway for mitochondrial quality control: Mitochondrial-derived vesicles
Sugiura, A., McLelland, G., Fon, E. A., & McBride, H. M. (2014) · The EMBO Journal · doi:10.15252/embj.201488104 · Cited by 862
Self-citationParkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65
Kazlauskaite, A., Kondapalli, C., Gourlay, R., Campbell, D. G., Ritorto, M. S., Hofmann, K., Alessi, D. R., Knebel, A., Trost, M., & Muqit, M. M. K. (2014) · Biochemical Journal · doi:10.1042/bj20140334 · Cited by 806
Mitofusin 1 and 2 play distinct roles in mitochondrial fusion reactions via GTPase activity
Ishihara, N., Eura, Y., & Mihara, K. (2004) · Journal of Cell Science · doi:10.1242/jcs.01565 · Cited by 731 · cited 6×
“Our observation of a steady-state ~500 kDa complex containing Mfn2 but not Mfn1 correlates with the reduced activity of the Mfn2 GTPase domain in comparison to Mfn1 (Ishihara et al., 2004), supports a distinct role for Mfn2 in OMM-ER tethering (Figure 3—figure supplement 1 and [de Brito and Scorrano, 2008]), and fits…”
BackgroundMethodInfluentialGandhi, S., Wood-Kaczmar, A., Yao, Z., Plun-Favreau, H., Deas, E., Klupsch, K., Downward, J., Latchman, D. S., Tabrizi, S. J., Wood, N. W., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.02.013 · Cited by 682
Cited by
Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease
Misrani, A., Tabassum, S., & Yang, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.617588 · Cited by 654
Mitochondrial dysfunction and mitophagy in parkinson’s disease: from mechanism to therapy
Malpartida, A. B., Williamson, M., Narendra, D. P., Wade-Martins, R., & Ryan, B. J. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.11.007 · Cited by 482
Quality control of the mitochondrion
Ng, M. Y. W., Wai, T., & Simonsen, A. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.02.009 · Cited by 445
Mitophagy in Alzheimer’s disease: Molecular defects and therapeutic approaches
Mary, A., Eysert, F., Checler, F., & Chami, M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01631-6 · Cited by 244
“Next, Parkin-dependent and PINK1 phosphoubiquitination of the ER-mitochondria tether MFN2 uncouples mitochondria and permits its engulfment and mitophagic degradation [55].”
Critical role of mitochondrial ubiquitination and the OPTN–ATG9A axis in mitophagy
Yamano, K., Kikuchi, R., Kojima, W., Hayashida, R., Koyano, F., Kawawaki, J., Shoda, T., Demizu, Y., Naito, M., Tanaka, K., et al. (2020) · Journal of Cell Biology · doi:10.1083/jcb.201912144 · Cited by 205
Metadata
- Authors
- McLelland, G.-L., Goiran, T., Yi, W., Dorval, G., Chen, C. X., Lauinger, N. D., Krahn, A. I., Valimehr, S., Rakovic, A., Rouiller, I., Durcan, T. M., Trempe, J.-F., & Fon, E. A.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2018-04-20
- Volume
- 7
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2800197308
- Cited by
- 381
- References
- 18
- FWCI
- 25.74
- Type
- journal article
- Language
- en
- Open access
- gold
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy. https://app.cochat.ai/papers/10.7554/elife.32866
- The paper
- McLelland, G.-L., Goiran, T., Yi, W., Dorval, G., Chen, C. X., Lauinger, N. D., Krahn, A. I., Valimehr, S., Rakovic, A., Rouiller, I., Durcan, T. M., Trempe, J.-F., & Fon, E. A. (2018). Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy. eLife. https://doi.org/10.7554/elife.32866
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
