The plasmodial apicoplast was retained under evolutionary selective pressure to assuage blood stage oxidative stress

Med Hypotheses. 2005;65(4):683-90. doi: 10.1016/j.mehy.2005.05.011.


Malaria, the clinical disease resulting from infection with Plasmodium, has haunted mankind with illness and death for thousands of years. As Plasmodia's ancient ancestor evolved from a mixotroph to an intracellular parasite, subsiding on amino acids obtained from hemoglobin, it encountered increased oxidative stress. To compensate for this oxidative stress, Plasmodia reduced its own production of reactive oxygen species by becoming largely fermentative and adapted novel methods to assuage oxidative injury. One such method appears to have been accomplished through the acquisition, retention and exploitation of an ancient red algal endosymbiote, now denoted the apicoplast. The apicoplast, located in close proximity to mitochondria, appears to synthesize the potent antioxidant lipoic acid. Lipoic acid may be utilized by Plasmodium as an antioxidant, a shuttle for reducing potentials and as a mitochondrial cofactor. Inhibition or alteration of the apicoplast leads to a curious phenomena known as "delayed death", whereby parasites die not in the present generation but in the ensuing one. Apicoplast inhibition may produce lipoic acid "starvation", increasing oxidative stress/mitochondrial injury during the subsequent asexual reproductive cycle. Collectively, data available to date indicate that the apicoplast was retained as an obligate endosymbiote, under evolutionary selective pressure, to assuage oxidative stress and plays a critical role in maintaining parasite viability during the Plasmodial shizont blood stage.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antiprotozoal Agents / metabolism
  • Biological Evolution*
  • Organelles / metabolism
  • Organelles / physiology*
  • Oxidative Stress / physiology*
  • Plasmodium / physiology*
  • Selection, Genetic*
  • Symbiosis*
  • Thioctic Acid / metabolism


  • Antioxidants
  • Antiprotozoal Agents
  • Thioctic Acid