The mitochondrial ubiquitin ligase MARCH5 resolves MAVS aggregates during antiviral signalling.
作者： Young-Suk Yoo , Yong-Yea Park , Jae-Hoon Kim , Hyeseon Cho , Song-Hee Kim
DOI: 10.1038/NCOMMS8910
关键词:
摘要: Mitochondria serve as platforms for innate immunity. The mitochondrial antiviral signalling (MAVS) protein forms aggregates that elicit robust type-I interferon induction on viral infection, but persistent MAVS leads to host immunopathology; it remains unknown how these are resolved. Here we identify the mitochondria-resident E3 ligase, MARCH5, a negative regulator of aggregates. March5(+/-) mice and MARCH5-deficient immune cells exhibit low replication elevated responses RNA viruses. MARCH5 binds only during stimulation when aggregates, interactions require RING domain CARD MAVS. not its mutant (MARCH5(H43W)), reduces level transfers ubiquitin Lys7 Lys500 promotes proteasome-mediated degradation. Our results indicate modulates MAVS-mediated signalling, preventing excessive reactions.
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