title: Phosphatidic acid (PA)-preferring phospholipase A1 regulates mitochondrial dynamics.
abstract: Recent studies have suggested that phosphatidic acid (PA), a cone-shaped phospholipid that can generate negative curvature of lipid membranes, participates in mitochondrial fusion. However, precise mechanisms underling the production and consumption of PA on the mitochondrial surface are not fully understood. Phosphatidic acid-preferring phospholipase A1 (PA-PLA1)/DDHD1 is the first identified intracellular phospholipase A1 and preferentially hydrolyzes PA in vitro. Its cellular and physiological functions have not been elucidated. In this study, we show that PA-PLA1 regulates mitochondrial dynamics. PA-PLA1, when ectopically expressed in HeLa cells, induced mitochondrial fragmentation, whereas its depletion caused mitochondrial elongation. The effects of PA-PLA1 on mitochondrial morphology appear to counteract those of MitoPLD, a mitochondrion-localized phospholipase D that produces PA from cardiolipin. Consistent with high levels of expression of PA-PLA1 in testis, PA-PLA1 knock-out mice have a defect in sperm formation. In PA-PLA1-deficient sperm, the mitochondrial structure is disorganized, and an abnormal gap structure exists between the middle and principal pieces. A flagellum is bent at that position, leading to a loss of motility. Our results suggest a possible mechanism of PA regulation of the mitochondrial membrane and demonstrate an in vivo function of PA-PLA1 in the organization of mitochondria during spermiogenesis.
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Baba
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Kashiwagi
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Nagisa
authors.initials: N
authors.lastname: Arimitsu
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kogure
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Edo
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Research Center for Biosignal, Akita University, Akita 010-8543, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.affiliation: Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Pharmacology and Center for Developmental Genetics, Stony Brook University, Stony Brook, New York 11794-5140, and.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
authors.affiliation: Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan.
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan,. Electronic address: tani@toyaku.ac.jp.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Tani
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000235:genetics / Q000378:metabolism; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism; D013082:Sperm Tail / Q000201:enzymology*; D013091:Spermatogenesis / Q000502:physiology*
chemical_list: D002308:Cardiolipins; D024101:Mitochondrial Proteins; D010712:Phosphatidic Acids; D010711:Phosphatidate Phosphatase; D010739:Phospholipase D; C558126:mitoPLD protein, mouse
keywords: Membrane; Mitochondria; Phosphatidic Acid; Phospholipase A; Sperm