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Misregulation of a DDHD Domain-containing Lipase Causes Mitochondrial Dysfunction in Yeast.

Pradeep Kumar, Yadav and Ram, Rajasekharan (2016) Misregulation of a DDHD Domain-containing Lipase Causes Mitochondrial Dysfunction in Yeast. The Journal of Biological Chemistry, 291 (35). pp. 18562-18581.

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The DDHD domain-containing proteins, which belong to the intracellular phospholipase A1 (iPLA1) family, have been predicted to be involved in phospholipid metabolism, lipid trafficking, membrane turnover, and signaling. Defective cardiolipin (CL), phosphatidylethanolamine, and phosphatidylglycerol remodeling cause Barth syndrome and mitochondrial dysfunction. Here, we report that Yor022c is a Ddl1 (DDHD domaincontaining lipase 1) that hydrolyzes CL, phosphatidylethanolamine, and phosphatidylglycerol. Ddl1 has been implicated in the remodeling of mitochondrial phospholipids and CL degradation. Our data also suggested that the accumulation of monolysocardiolipin is deleterious to the cells.Weshow that Aft1 and Aft2 transcription factors antagonistically regulate the DDL1 gene. This study reveals that the misregulation of DDL1 by Aft1/2 transcription factors alters CL metabolism and causes mitochondrial dysfunction in the cells. In humans, mutations in theDDHD1andDDHD2genes cause specific types of hereditary spastic paraplegia (SPG28 and SPG54, respectively), and the yeast DDL1-defective strain produces similar phenotypes of hereditary spastic paraplegia (mitochondrial dysfunction and defects in lipid metabolism). Therefore, the DDL1-defective strain could be a good model system for understanding hereditary spastic paraplegia.

Item Type: Article
Uncontrolled Keywords: mitochondrial dysfunction, yeast, lipid metabolism, DDHD domain
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 22 Lipid Chemistry
500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology
Divisions: Dept. of Lipid Science
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 09 Jan 2018 10:34
Last Modified: 09 Jan 2018 10:34
URI: http://ir.cftri.com/id/eprint/13269

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