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Mitochondrial translocation of TFEB regulates complex I and inflammation
Mitochondrial translocation of TFEB regulates complex I and inflammation
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Length:
20 minutes
Released:
Feb 28, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.02.27.530219v1?rss=1
Authors: Calabrese, C., Nolte, H., Pitman, M. R., Ganesan, R., Lampe, P., Laboy, R., Ripa, R., Fischer, J., Chipurupalli, S., Gutierrez, S., Polara, R., Thomas, D., Pitson, S. M., Antebi, A., Robinson, N.
Abstract:
TFEB is a master regulator of autophagy, lysosome biogenesis and mitochondrial metabolism that works, and immunity, primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomic analysis revealed extensive TFEB co-precipitation with several mitochondrial proteins, whose interactions are disrupted upon infection with S. Typhimurium. Localization of TFEB in the mitochondrial matrix was confirmed by high resolution confocal microscopy and biochemistry with translocation dependent on a conserved N-terminal TOMM20-binding motif enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis.
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http://biorxiv.org/cgi/content/short/2023.02.27.530219v1?rss=1
Authors: Calabrese, C., Nolte, H., Pitman, M. R., Ganesan, R., Lampe, P., Laboy, R., Ripa, R., Fischer, J., Chipurupalli, S., Gutierrez, S., Polara, R., Thomas, D., Pitson, S. M., Antebi, A., Robinson, N.
Abstract:
TFEB is a master regulator of autophagy, lysosome biogenesis and mitochondrial metabolism that works, and immunity, primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomic analysis revealed extensive TFEB co-precipitation with several mitochondrial proteins, whose interactions are disrupted upon infection with S. Typhimurium. Localization of TFEB in the mitochondrial matrix was confirmed by high resolution confocal microscopy and biochemistry with translocation dependent on a conserved N-terminal TOMM20-binding motif enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Feb 28, 2023
Format:
Podcast episode
Titles in the series (100)
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