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Burkholderia pseudomallei BipD initiates mitophagy to evade killing by hijacking host KLHL9-KLHL13-CUL3 E3 ligase to ubiquitinate IMMT.

Dongqi NanXuhu MaoQian Li
Published in: Autophagy (2024)
Burkholderia pseudomallei ( B. pseudomallei ) is a facultative intracellular parasitic pathogen with multiple immune escape mechanisms. Mitophagy is critical for mitochondrial quality control and function in various biological processes. We reported that B. pseudomallei infection induces mitophagy to promote its intracellular survival by decreasing mitochondrial reactive oxygen species (mtROS). Mechanically, B. pseudomallei infection leads to the rupture of host outer mitochondrial membrane (OMM) by DNM1L/DRP1 (dynamin 1-like). Furthermore, BipD, the type III secretion system (T3SS) needle tip protein of B. pseudomallei , hijacks the host KLHL9 (kelch-like 9)-KLHL13 (kelch-like 13)-CUL3 (cullin 3) E3 ubiquitin ligase complex to promote the K63-linked ubiquitination of IMMT/mitofilin (inner membrane protein, mitochondrial) at the K211 site. Then BipD-initiated mitophagy, via the conventional macroautophagy/autophagy pathway with the receptor SQSTM1 (sequestosome 1) involvement, decreases the mtROS production, which in turn facilitates the intracellular survival of B. pseudomallei . Here, our findings reveal an unexpected function of BipD and the KLHL9-KLHL13-CUL3 E3 ligase complex and suggest a novel mechanism used by bacterial pathogens that hijack host mitophagy for their survival.
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