The conserved AAA-ATPase Msp1 confers organelle specificity to tail-anchored proteins.
نویسندگان
چکیده
The accuracy of tail-anchored (TA) protein targeting to the endoplasmic reticulum (ER) depends on the Guided Entry of Tail-Anchored (Get) protein targeting machinery. The fate of TA proteins that become inappropriately inserted into other organelles, such as mitochondria, is unknown. Here, we identify Msp1, a conserved, membrane-anchored AAA-ATPase (ATPase associated with a variety of cellular activities) that localizes to mitochondria and peroxisomes, as a critical factor in a quality control pathway that senses and degrades TA proteins mistargeted to the outer mitochondrial membrane (OMM). Pex15 is normally targeted by the Get pathway to the ER, from where it travels to peroxisomes. Loss of Msp1 or loss of the Get pathway results in the redistribution of Pex15 to mitochondria. Cells lacking both a functional Get pathway and Msp1 accumulate increased amounts of Pex15 on the OMM and display severely dysfunctional mitochondrial morphology. In addition, Msp1 binds and promotes the turnover of a Pex15 mutant that is misdirected to the OMM. Our data suggest that Msp1 functions in local organelle surveillance by extracting mistargeted proteins, ensuring the fidelity of organelle specific-localization of TA proteins.
منابع مشابه
The AAA protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane
Msp1 is a conserved AAA ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-induci...
متن کاملTitle: The AAA Protein Msp1 Mediates Clearance of Excess Tail-Anchored Proteins from the Peroxisomal Membrane
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 111 22 شماره
صفحات -
تاریخ انتشار 2014