Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics
Peroxisomes are highly dynamic and responsive organelles, which can adjust their morphology, number, intracellular position, and metabolic functions according to cellular needs. Peroxisome multiplication in mammalian cells involves the concerted action of the membrane-shaping protein PEX11β and divi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/12/1922 |
| _version_ | 1797488944191897600 |
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| author | Ruth E. Carmichael Markus Islinger Michael Schrader |
| author_facet | Ruth E. Carmichael Markus Islinger Michael Schrader |
| author_sort | Ruth E. Carmichael |
| collection | DOAJ |
| description | Peroxisomes are highly dynamic and responsive organelles, which can adjust their morphology, number, intracellular position, and metabolic functions according to cellular needs. Peroxisome multiplication in mammalian cells involves the concerted action of the membrane-shaping protein PEX11β and division proteins, such as the membrane adaptors FIS1 and MFF, which recruit the fission GTPase DRP1 to the peroxisomal membrane. The latter proteins are also involved in mitochondrial division. Patients with loss of DRP1, MFF or PEX11β function have been identified, showing abnormalities in peroxisomal (and, for the shared proteins, mitochondrial) dynamics as well as developmental and neurological defects, whereas the metabolic functions of the organelles are often unaffected. Here, we provide a timely update on peroxisomal membrane dynamics with a particular focus on peroxisome formation by membrane growth and division. We address the function of PEX11β in these processes, as well as the role of peroxisome–ER contacts in lipid transfer for peroxisomal membrane expansion. Furthermore, we summarize the clinical phenotypes and pathophysiology of patients with defects in the key division proteins DRP1, MFF, and PEX11β as well as in the peroxisome–ER tether ACBD5. Potential therapeutic strategies for these rare disorders with limited treatment options are discussed. |
| first_indexed | 2024-03-10T00:10:30Z |
| format | Article |
| id | doaj.art-cebe9d8b8ba64da686b0355b5e006543 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:10:30Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cebe9d8b8ba64da686b0355b5e0065432023-11-23T16:01:33ZengMDPI AGCells2073-44092022-06-011112192210.3390/cells11121922Fission Impossible (?)—New Insights into Disorders of Peroxisome DynamicsRuth E. Carmichael0Markus Islinger1Michael Schrader2College of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter EX4 4QD, UKInstitute of Neuroanatomy, Mannheim Centre for Translational Neuroscience, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, GermanyCollege of Life and Environmental Sciences, Biosciences, University of Exeter, Exeter EX4 4QD, UKPeroxisomes are highly dynamic and responsive organelles, which can adjust their morphology, number, intracellular position, and metabolic functions according to cellular needs. Peroxisome multiplication in mammalian cells involves the concerted action of the membrane-shaping protein PEX11β and division proteins, such as the membrane adaptors FIS1 and MFF, which recruit the fission GTPase DRP1 to the peroxisomal membrane. The latter proteins are also involved in mitochondrial division. Patients with loss of DRP1, MFF or PEX11β function have been identified, showing abnormalities in peroxisomal (and, for the shared proteins, mitochondrial) dynamics as well as developmental and neurological defects, whereas the metabolic functions of the organelles are often unaffected. Here, we provide a timely update on peroxisomal membrane dynamics with a particular focus on peroxisome formation by membrane growth and division. We address the function of PEX11β in these processes, as well as the role of peroxisome–ER contacts in lipid transfer for peroxisomal membrane expansion. Furthermore, we summarize the clinical phenotypes and pathophysiology of patients with defects in the key division proteins DRP1, MFF, and PEX11β as well as in the peroxisome–ER tether ACBD5. Potential therapeutic strategies for these rare disorders with limited treatment options are discussed.https://www.mdpi.com/2073-4409/11/12/1922peroxisomesmitochondriaorganelle dynamicsdivision defectsdynamin-related protein 1mitochondrial fission factor |
| spellingShingle | Ruth E. Carmichael Markus Islinger Michael Schrader Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics Cells peroxisomes mitochondria organelle dynamics division defects dynamin-related protein 1 mitochondrial fission factor |
| title | Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics |
| title_full | Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics |
| title_fullStr | Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics |
| title_full_unstemmed | Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics |
| title_short | Fission Impossible (?)—New Insights into Disorders of Peroxisome Dynamics |
| title_sort | fission impossible new insights into disorders of peroxisome dynamics |
| topic | peroxisomes mitochondria organelle dynamics division defects dynamin-related protein 1 mitochondrial fission factor |
| url | https://www.mdpi.com/2073-4409/11/12/1922 |
| work_keys_str_mv | AT ruthecarmichael fissionimpossiblenewinsightsintodisordersofperoxisomedynamics AT markusislinger fissionimpossiblenewinsightsintodisordersofperoxisomedynamics AT michaelschrader fissionimpossiblenewinsightsintodisordersofperoxisomedynamics |