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論文
タイトル
タイトル(英)
Cleaved PGAM5 dephosphorylates nuclear serine/arginine-rich proteins during mitophagy.
参照URL
https://researchmap.jp/N-Matsuda/published_papers/32869870
著者
著者(英)
Taiki Baba,Susumu Tanimura,Ayane Yamaguchi,Koichiro Horikawa,Masashi Yokozeki,Saki Hachiya,Shun-Ichiro Iemura,Tohru Natsume,Noriyuki Matsuda,Kohsuke Takeda
概要
概要(英)
PGAM5 is a protein phosphatase located in the inner mitochondrial membrane through its transmembrane (TM) domain and is cleaved within the TM domain upon mitochondrial dysfunction. We found previously that cleaved PGAM5 is released from mitochondria, following proteasome-mediated rupture of the outer mitochondrial membrane during mitophagy, a selective form of autophagy specific to mitochondria. Here, we examined the role of cleaved PGAM5 outside mitochondria. Deletion mutants that mimic cleaved PGAM5 existed not only in the cytosol but also in the nucleus, and a fraction of cleaved PGAM5 translocated to the nucleus during mitophagy induced by the uncoupler CCCP. We identified serine/arginine-related nuclear matrix protein of 160 kDa (SRm160)/SRRM1, which contains a highly phosphorylated domain rich in arginine/serine dipeptides, called the RS domain, as a nuclear protein that interacts with PGAM5. PGAM5 dephosphorylated SRm160, and incubation of lysates from WT cells, but not of those from PGAM5-deficient cells, induced dephosphorylation of SRm160 and another RS domain-containing protein SRSF1, one of the most characterized serine/arginine-rich (SR) proteins. Moreover, phosphorylation of these proteins and other SR proteins, which are commonly reactive toward the 1H4 monoclonal antibody that detects phosphorylated SR proteins, decreased during mitophagy, largely because of PGAM5 activity. These results suggest that PGAM5 regulates phosphorylation of these nuclear proteins during mitophagy. Because SRm160 and SR proteins play critical roles in mRNA metabolism, PGAM5 may coordinate cellular responses to mitochondrial stress at least in part through post-transcriptional and pre-translational events.
出版者・発行元
出版者・発行元(英)
誌名
誌名(英)
Biochimica et biophysica acta. Molecular cell research
1868
7
開始ページ
119045
終了ページ
119045
出版年月
2021年6月
査読の有無
査読有り
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
DOI URL
https://doi.org/10.1016/j.bbamcr.2021.119045
共同研究・競争的資金等の研究課題
研究者
松田 憲之 (マツダ ノリユキ)