title: Mitochondria: FKBP38 and mitochondrial degradation.
abstract: FK506-binding protein 38 (FKBP38) is a membrane chaperone that is localized predominantly to mitochondria and contains a COOH-terminal tail anchor. FKBP38 also harbors an FKBP domain that confers peptidyl-prolyl cis-trans isomerase activity, but it differs from other FKBP family members in that this activity is dependent on the binding of Ca(2+)-calmodulin. FKBP38 inhibits apoptosis by recruiting the anti-apoptotic proteins Bcl-2 and Bcl-xL to mitochondria. Mice deficient in FKBP38 die soon after birth manifesting a defect in neural tube closure that results in part from unrestrained apoptosis. We recently found that FKBP38 and Bcl-2 translocate from mitochondria to the endoplasmic reticulum during mitophagy, a form of autophagy responsible for the elimination of damaged mitochondria. FKBP38 and Bcl-2 thus escape the degradative fate of most mitochondrial proteins during mitophagy. This escape of FKBP38 is dependent on the low basicity of its COOH-terminal sequence and is essential for the suppression of apoptosis during mitophagy. FKBP38 thus plays a key role in the regulation of apoptosis under normal and pathological conditions.
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: smichi@bioreg.kyushu-u.ac.jp.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shirane-Kitsuji
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology*; D018832:Molecular Chaperones / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*
chemical_list: C471205:FKBP8 protein, human; C119437:Fkbp8 protein, mouse; D018832:Molecular Chaperones; D022021:Tacrolimus Binding Proteins
keywords: Apoptosis; Endoplasmic reticulum; FKBP38; Mitochondria; Mitophagy