Does Mitochondrial Fusion Require Transmembrane Potential?
I E Karavaeva1, K V Shekhireva, F F Severin
1Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119992, Russia.
Abstract:
Dissipation of transmembrane potential inhibits mitochondrial fusion and thus prevents reintegration of damaged mitochondria into the mitochondrial network. Consequently, damaged mitochondria are removed by autophagy. Does transmembrane potential directly regulate the mitochondrial fusion machinery? It was shown that inhibition of ATP-synthase induces fragmentation of mitochondria while preserving transmembrane potential. Moreover, mitochondria of the yeast Saccharomyces cerevisiae retain the ability to fuse even in the absence of transmembrane potential. Metazoan mitochondria in some cases retain ability to fuse for a short period even in a depolarized state. It also seems unlikely that transmembrane potential-based regulation of mitochondrial fusion would prevent reintegration of mitochondria with damaged ATP-synthase into the mitochondrial network. Such reintegration could lead to clonal expansion of mtDNAs harboring deleterious mutations in ATP synthase. We speculate that transmembrane potential is not directly involved in regulation of mitochondrial fusion but affects mitochondrial NTP/NDP ratio, which in turn regulates their fusion.
Insights
Transmembrane potential does not directly regulate mitochondrial fusion. Instead, it influences the NTP/NDP ratio, which then controls the fusion process, ensuring proper mitochondrial network maintenance.
Area of Science:
- Cell Biology
- Mitochondrial Dynamics
- Autophagy
Background:
- Mitochondrial fusion integrates damaged mitochondria into the network; loss of transmembrane potential inhibits this.
- Damaged mitochondria are typically removed via autophagy.
- The direct role of transmembrane potential in regulating mitochondrial fusion machinery is unclear.
Purpose of the Study:
- To investigate whether transmembrane potential directly regulates mitochondrial fusion.
- To explore the relationship between mitochondrial integrity, fusion, and transmembrane potential.
Main Methods:
- Analysis of mitochondrial fragmentation upon ATP-synthase inhibition while preserving transmembrane potential.
- Observation of mitochondrial fusion capabilities in yeast and metazoan cells under depolarized conditions.
Main Results:
- Inhibition of ATP-synthase causes mitochondrial fragmentation without affecting transmembrane potential.
- Yeast mitochondria can fuse even without transmembrane potential.
- Metazoan mitochondria may retain fusion ability briefly in a depolarized state.
Conclusions:
- Transmembrane potential likely does not directly regulate mitochondrial fusion machinery.
- Regulation may occur indirectly via the mitochondrial NTP/NDP ratio.
- This indirect regulation prevents the reintegration of mitochondria with damaged ATP-synthase, avoiding deleterious mtDNA mutation expansion.
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