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Defining Trafficking Steps Required for Cardiolipin Remodeling
Author(s) -
Baile Matthew G,
Whited Kevin,
Claypool Steven M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.585.14
Subject(s) - cardiolipin , intermembrane space , inner mitochondrial membrane , inner membrane , microbiology and biotechnology , chemistry , translocase of the inner membrane , mitochondrion , electrochemical gradient , translocase of the outer membrane , mitochondrial intermembrane space , biophysics , bacterial outer membrane , membrane , biology , biochemistry , mitochondrial membrane transport protein , phospholipid , escherichia coli , gene
The phospholipid cardiolipin (CL) is required for numerous mitochondrial processes. After its de novo synthesis on the matrix‐facing leaflet of the inner membrane, CL undergoes acyl chain remodeling to achieve its final form. In yeast, this process is completed by the transacylase tafazzin which associates with intermembrane space‐facing membranes via a membrane anchor that does not traverse the lipid bilayer. To gain insight into the topology of CL remodeling, we examined the submitochondrial localization of Cld1p, the lipase that initiates CL remodeling. We show that Cld1p is associated with the matrix‐facing leaflet of the mitochondrial inner membrane. Thus, once generated by Cld1p, monolyso‐CL must be transported to the intermembrane space‐facing leaflets of the inner or outer membrane to gain access to tafazzin, identifying a previously unknown step in the CL remodeling pathway. Additionally, we examined the regulation of CL remodeling. Cld1p expression and function are augmented in growth conditions requiring mitochondrially produced energy. Interestingly, selectively diminishing either the electrical or chemical gradients across the inner membrane with ionophores indicates that function of either the MLCL transporter or tafazzin does not requires an intact proton‐motive force. In contrast, the function of Cld1p is enhanced upon diminution of either aspect of electrochemical gradient. This work was supported by National Institutes of Health grant number R00HL089185 to SMC. MGB is a predoctoral fellow of the American Heart Association.