Cardiolipin-Mediated Mitochondrial Dynamics and Stress Response inArabidopsis   

Abstract

Mitochondria are essential and dynamic organelles in eukaryotes. Cardiolipin (CL) is a key phospholipid in mitochondrial membranes, playing important roles in maintaining the functional integrity and dynamics of mitochondria in animals and yeasts. However, CL's role in plants is just beginning to be elucidated. In this study, we used Arabidopsis thaliana to examine the subcellular distribution of CL and CARDIOLIPIN SYNTHASE (CLS) and analyzed loss-of-function cls mutants for defects in mitochondrial morphogenesis and stress response. We show that CL localizes to mitochondria and is enriched at specific domains, and CLS targets to the inner membrane of mitochondria with its C terminus in the intermembrane space. Furthermore, cls mutants exhibit significantly impaired growth as well as altered structural integrity and morphogenesis of mitochondria. In contrast to animals and yeasts, in which CL's effect on mitochondrial fusion is more profound, Arabidopsis CL plays a dominant role in mitochondrial fission and exerts this function, at least in part, through stabilizing the protein complex of the major mitochondrial fission factor, DYNAMIN-RELATED PROTEIN3. CL also plays a role in plant responses to heat and extended darkness, stresses that induce programmed cell death. Our study has uncovered conserved and plant-specific aspects of CL biology in mitochondrial dynamics and the organism response to environmental stresses.

Cardiolipin at the heart of stress response across kingdoms

“…Atcls mutants harbor some of the features of yeast and mammal CL-deficient cells, such as low abundance of CI/CIII supercomplexes and abnormal mitochondria with few cristae. 16,17 Moreover giant mitochondria were observed suggesting deficiency of the plant mitochondrial fusion/fission machinery, 16,17 confirming previous results obtained in animals and yeast. [18][19][20] More specifically it was found that CL plays a dominant role in mitochondrial fission through the major mitochondrial fission factor, DYNAMIN-RELATED PROTEIN3 (DRP3).…”

“…[18][19][20] More specifically it was found that CL plays a dominant role in mitochondrial fission through the major mitochondrial fission factor, DYNAMIN-RELATED PROTEIN3 (DRP3). 16 These reports highlight the central role of CL in maintaining mitochondrial structure and function in yeast, plants, and animals. However, in contrast to yeast crd1 mutant, Atcls seedlings are severely affected, both in their growth and their development, 16,17 suggesting a broader role for CL in plant cell functioning.…”

“…16 These reports highlight the central role of CL in maintaining mitochondrial structure and function in yeast, plants, and animals. However, in contrast to yeast crd1 mutant, Atcls seedlings are severely affected, both in their growth and their development, 16,17 suggesting a broader role for CL in plant cell functioning.…”

“…4 In cells from Barth syndrome patients, reduced CL content leads to mitochondrial dysfunction and pathological conditions. 14,15 Very recently, cls T-DNA insertion knockdown 16 and knockout 17 mutants have been characterized in Arabidopsis. Atcls mutants harbor some of the features of yeast and mammal CL-deficient cells, such as low abundance of CI/CIII supercomplexes and abnormal mitochondria with few cristae.…”

“…In plants, where the release of cytochrome c from mitochondria has also been described during PCD, 35,36 the impact of CLS downregulation on stress susceptibility has been tested on both whole plants of RNAi lines 16 and protoplasts from cls mutants. 17 In both cases cls defective mutants displayed a much higher susceptibility to stress, as in animals where cardiolipin deficiency Figure 1.…”