Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission
Open accessAbstract
Several mitochondrial outer membrane proteins—mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (Mff), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51, respectively)—have been proposed to promote mitochondrial fission by recruiting the GTPase dynamin-related protein 1 (Drp1), but fundamental issues remain concerning their function. A recent study supported such a role for Mff but not for Fis1. In addition, it is unclear whether MiD49 and MiD51 activate or inhibit fission, because their overexpression causes extensive mitochondrial elongation. It is also unknown whether these proteins can act in the absence of one another to mediate fission. Using Fis1-null, Mff-null, and Fis1/Mff-null cells, we show that both Fis1 and Mff have roles in mitochondrial fission. Moreover, immunofluorescence analysis of Drp1 suggests that Fis1 and Mff are important for the number and size of Drp1 puncta on mitochondria. Finally, we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. These results demonstrate that multiple receptors can recruit Drp1 to mediate mitochondrial fission.
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MIEF1/MiD51 and MIEF2/MiD49 recruit DRP1 to mitochondria independent of MFF, but inhibit DRP1 GTPase activity, leading to mitochondrial elongation when overexpressed.
“MIEF1/MiD51 and the variant MIEF2/MiD49 recruit DRP1 to mitochondria independent of MFF, but in contrast to MFF, inhibit DRP1 GTPase activity leading to mitochondrial elongation when MiD49/51 is overexpressed [92, 95, 96].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [96]
Other factors such as mitochondrial fission factor (Mff) or mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51) can also mediate DRP1 recruitment in absence of FIS1.
“other factors such as mitochondrial fission factor (Mff) or mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51) can also mediate DRP1 recruitment in absence of FIS1 (Loson et al., 2013; Shen et al., 2014)”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Loson et al., 2013
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- Authors
- Losón, O. C., Song, Z., Chen, H., & Chan, D. C.
- Affiliations
- California Institute of Technology (US)
- Corresponding author
- Chan, David C.
- Venue
- Molecular Biology of the Cell
- Published
- 2013-03
- Volume
- 24
- Issue
- 5
- Pages
- 659-667
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC3583668
- OpenAlex
- W2143688500
- Cited by
- 1,235
- References
- 29
- Citations by year
- 2026: 85 · 2025: 102 · 2024: 121 · 2023: 110 · 2022: 136 · 2021: 122 · 2020: 105 · 2019: 90 · 2018: 89 · 2017: 79 · 2016: 81 · 2015: 51 · 2014: 45 · 2013: 18
- FWCI
- 29.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health (5f31gm089327-02)
- National Institute of General Medical Sciences (R01GM062967, GM062967, 5F31GM089327, F31 GM089327)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- mitochondrial fission, Drp1, Fis1, Mff, MiD51, mitochondrial outer membrane proteins, mitochondrial dynamics
- MeSH terms
- Animals, Fibroblasts, HeLa Cells, Humans, Membrane Proteins, Microtubule-Associated Proteins, Peptide Elongation Factors, Mitochondrial Proteins, Dynamins, RNA, Small Interfering, Mitochondrial Membranes, Mice, Mitochondrial Dynamics
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