Wednesday, 8 April 2015

Cardiolipin is a key determinant for mtDNA stability and segregation during mitochondrial stress

Luis Alberto Luévano-Martínez,Maria Fernanda Forni,Valquiria Tiago dos Santos,Nadja C. Souza-Pinto and Alicia J. Kowaltowski

Cardiolipin makes up about 15% of the phospholipid content of the mitochondrial inner membrane. Cardiolipin is known to stabilize ATP synthase dimers and respiratory chain super complexes, and is able to promote cristae-like structures by responding to pH gradients.

In this paper, they investigate the role of cardiolipin in the cellular response to mitochondrial stress in yeast. A genetic model which lacks the cardiolipin synthase gene is used.

Results show that cells lacking cardiolipin have increased levels of PG, the precursor of cardiolipin. In optimal growth conditions, cells without cardiolipin show no defects in respiration, whereas under thermal stress these cells show decreases in both basal and maximal respiratory rates. Thermal stress reduces the amount of respiratory chain complexes, including subunits encoded by mtDNA, this suggests that lack of cardiolipin may lead to mtDNA instability. Further results suggest that mtDNA indeed becomes more prone to stress-induced damage when no cardiolipin is present.
Cardiolipin may be involved in mtDNA segregation during budding.

MtDNA is normally anchored to the inner membrane, and perhaps cardiolipin plays a role in this anchoring. The inner membrane of mitochondria in yeast in composed of phosphatidylcholine (PC, about 38%), phosphatidylethanolamine (PE, 24 %), phosphatidylinositol (16%), cardiolipin (16%), phosphatidylserine (PS, 4%) and phosphoatidic acid (1.5%). In the paper they show that isolated nucleoids bind more to cardiolipin than to its precursor PG. No significant binding is observed to PC. Also when nucleoids isolated from mammalian cell lines were used, affinity for binding to cardiolipin was higher than binding to any of the other phospholipids. Further results suggest that mtDNA can anchor to the inner membrane in the absence of cardiolipin under control conditions, but not under thermal stress.

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