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Published on: September 30, 2012
Compositionally unique mitochondria in filopodia support cellular migration
Madeleine Marlar-Pavey1, Daniel Tapias-Gomez1, Marcel Mettlen1
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.
Abstract:
Local metabolic demand within cells varies widely and the extent to which individual mitochondria can be specialized to meet these functional needs is unclear. We examined the subcellular distribution of MICOS, a spatial and functional organizer of mitochondria, and discovered that it dynamically enriches at the tip of a minor population of mitochondria in the cell periphery that we term "METEORs". METEORs have a unique composition; MICOS enrichment sites are depleted of mtDNA and matrix proteins and contain high levels of the Ca2+ uniporter MCU, suggesting a functional specialization. METEORs are also enriched for the myosin MYO19, which promotes their trafficking to a small subset of filopodia. We identify a positive correlation between the length of filopodia and the presence of METEORs and show that elimination of mitochondria from filopodia impairs cellular motility. Our data reveal a novel type of mitochondrial heterogeneity and suggest compositionally specialized mitochondria support cell migration.
Insights
Mitochondria can specialize, with unique peripheral mitochondria (METEORs) supporting cell migration. These specialized mitochondria, enriched with MICOS and MCU, traffic to filopodia, enhancing cellular motility.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Cell Motility
Background:
- Cellular metabolic demands vary, necessitating functional specialization of mitochondria.
- The extent of mitochondrial specialization and their role in cell migration remains largely unknown.
Purpose of the Study:
- To investigate the subcellular distribution and functional specialization of mitochondria.
- To identify novel mitochondrial subpopulations and their role in cell migration.
Main Methods:
- Subcellular fractionation and immunofluorescence microscopy to analyze MICOS distribution.
- Mitochondrial DNA (mtDNA) and matrix protein content analysis.
- Expression analysis of calcium uniporter (MCU) and myosin MYO19.
- Live-cell imaging of mitochondrial trafficking to filopodia.
- Functional assays assessing cellular motility upon mitochondrial manipulation.
Main Results:
- A novel subpopulation of peripheral mitochondria, termed METEORs (Mitochondria Enriched in the Cell Periphery), was identified.
- METEORs are characterized by MICOS enrichment, mtDNA and matrix protein depletion, and high MCU levels.
- METEORs are associated with myosin MYO19 and traffic to filopodia.
- The presence of METEORs in filopodia positively correlates with filopodia length.
- Elimination of mitochondria from filopodia impairs cell migration.
Conclusions:
- Mitochondria exhibit heterogeneity, with specialized subpopulations like METEORs.
- Compositionally specialized mitochondria, particularly METEORs, play a crucial role in supporting cell migration.
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