Cardiolipin deficiency leads to decreased cardiolipin peroxidation and increased resistance of cells to apoptosis

Z Huang, J Jiang, VA Tyurin, Q Zhao, A Mnuskin… - Free Radical Biology …, 2008 - Elsevier
Z Huang, J Jiang, VA Tyurin, Q Zhao, A Mnuskin, J Ren, NA Belikova, W Feng, IV Kurnikov
Free Radical Biology and Medicine, 2008Elsevier
Cardiolipin (CL), a unique mitochondrial phospholipid synthesized by CL synthase (CLS),
plays important, yet not fully understood, roles in mitochondria-dependent apoptosis. We
manipulated CL levels in HeLa cells by knocking down CLS using RNA interference and
selected a clone of CL-deficient cells with~ 45% of its normal content. ESI–MS analysis
showed that the CL molecular species were the same in CL-deficient and CL-sufficient cells.
CL deficiency did not change mitochondrial functions (membrane potential, reactive oxygen …
Cardiolipin (CL), a unique mitochondrial phospholipid synthesized by CL synthase (CLS), plays important, yet not fully understood, roles in mitochondria-dependent apoptosis. We manipulated CL levels in HeLa cells by knocking down CLS using RNA interference and selected a clone of CL-deficient cells with ~45% of its normal content. ESI–MS analysis showed that the CL molecular species were the same in CL-deficient and CL-sufficient cells. CL deficiency did not change mitochondrial functions (membrane potential, reactive oxygen species generation, cellular ATP levels) but conferred resistance to apoptosis induced by actinomycin D (ActD), rotenone, or γ-irradiation. During ActD-induced apoptosis, decreased CL peroxidation along with suppressed cytochrome (cyt) c release was observed in CL-deficient cells, whereas Bax translocation to mitochondria remained similar to that in CL-sufficient HeLa cells. The amounts of loosely bound cyt c (releasable under high ionic strength conditions) were the same in CL-deficient and CL-sufficient cells. Given that CL peroxidation during apoptosis is catalyzed by CL/cyt c complexes and CL oxidation products are essential for cyt c release from mitochondria, our results suggest that CL deficiency prevents adequate assembly of productive CL/cyt c complexes and CL peroxidation, resulting in increased resistance to apoptosis.
Elsevier