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Cells dispose of cytoplasmic mitochondrial DNA by nucleoid-phagy

Mitochondrial damage in stress conditions results in the release of mitochondrial DNA (mtDNA), causing inflammation that is linked to various diseases. We discovered a mechanism for the elimination of this harmful mtDNA — ‘nucleoid-phagy’. Targeting this process represents another way to treat mitochondrial damage-related diseases.

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Fig. 1: TFAM is an autophagy receptor for cytoplasmic mtDNA.

References

  1. Kim, J. et al. VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease. Science 366, 1531–1536 (2019). This paper reports that during oxidative stress the mtDNA is released via pores formed by voltage-dependent anion channel (VDAC) oligomers in the outer mitochondrial membrane.

  2. Liu, H. et al. Prohibitin 1 regulates mtDNA release and downstream inflammatory responses. EMBO J. 41, e111173 (2022). This paper reports that PHB1 is crucial for mtDNA release and inflammatory responses by regulating mitochondrial inner membrane permeability.

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This is a summary of: Liu, H. et al. TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA. Nat. Cell. Biol. https://doi.org/10.1038/s41556-024-01419-6 (2024).

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Cells dispose of cytoplasmic mitochondrial DNA by nucleoid-phagy. Nat Cell Biol 26, 849–850 (2024). https://doi.org/10.1038/s41556-024-01421-y

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