Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense (Nat Immunol. 2016, 17(9):1037-45.)

報告日期: 2017/03/21
報告時間: 4:00/4:50
報告學生: 謝翔麑
講評老師: 謝奇璋
附件下載: 下載[1619-1487728392-1.pdf] 

Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense

Nat Immunol.17(9):1037-45 (Sep 2016)

Speaker: Shiang-Ni Hsieh                   Date: 16:00-16:50, Mar 21, 2017

Commentator: Dr. Chi-Chang Shieh          Place: Room 602

Abstract

Macrophages scale their core metabolism after being activated by the Gram-negative bacteria through TLR- and NLRP3-dependent pathways, but the precise regulation of the mitochondrial electron-transport chain (ETC) and its functional implications are currently unknown. Mitochondria, a bioenergetic organelle of the metabolic pathways that not only contributes to energy supply, but also serves as a signaling platform for various innate immunological signaling pathways. From the previous study accumulate that TCA-cycle intermediates might directly contribute to macrophage antimicrobial functions1, and the catabolic processes converge on the mitochondrial electron- transport chain (ETC) with two electron carriers (coenzyme Q and cytochrome c) and four respiratory complexes (CI–CIV); these complexes, except for CII, can dynamically assemble as larger molecular super-complexes (SCs) in the mitochondrial inner membrane2. Whether super-assembly of ETC respiratory complexes can contribute to immunological function remains to be determined. Here the authors show the recognition of live bacteria by macrophages transiently decreased assembly of the ETC complex I (CI) and CI-containing super-complexes and switched the relative contributions of CI and CII to mitochondrial respiration. The induction of CII activity was not observed after phagocytosis of dead bacteria but was restored via bacterial RNA. Conversely, inhibition of CII during challenge with viable bacteria normalized the amount of IL-1 and IL-10 to that found after an encounter with dead bacteria. Our findings identify a critical role for the mitochondrial ETC in innate immune responses to bacterial infection and highlight potential therapeutic interest in manipulating the ETC.

References

  1. Tannahill, G.M. et al. Succinate is an inflammatory signal that induces IL-1through HIF-1. Nature    496, 238–242 (2013).
  2. Enríquez, J.A. Supramolecular organization of respiratory complexes. Annu. Rev. Physiol. 78, 533 561 (2016).