Mitochondrial biology and disease in Dictyostelium.
The cellular slime mold Dictyostelium discoideum has become an increasingly useful model for the study of mitochondrial biology and disease. Dictyostelium is an amoebazoan, a sister clade to the animal and fungal lineages. The mitochondrial biology of Dictyostelium exhibits some features which are unique, others which are common to all eukaryotes, and still others that are otherwise found only in the plant or the animal lineages. The AT-rich mitochondrial genome of Dictyostelium is larger than its mammalian counterpart and contains 56kb (compared to 17kb in mammals) encoding tRNAs, rRNAs, and 33 polypeptides (compared to 13 in mammals). It produces a single primary transcript that is cotranscriptionally processed into multiple monocistronic, dicistronic, and tricistronic mRNAs, tRNAs, and rRNAs. The mitochondrial fission mechanism employed by Dictyostelium involves both the extramitochondrial dynamin-based system used by plant, animal, and fungal mitochondria and the ancient FtsZ-based intramitochondrial fission process inherited from the bacterial ancestor. The mitochondrial protein-import apparatus is homologous to that of other eukaryote, and mitochondria in Dictyostelium play an important role in the programmed cell death pathways. Mitochondrial disease in Dictyostelium has been created both by targeted gene disruptions and by antisense RNA and RNAi inhibition of expression of essential nucleus-encoded mitochondrial proteins. This has revealed a regular pattern of aberrant mitochondrial disease phenotypes caused not by ATP insufficiency per se, but by chronic activation of the universal eukaryotic energy-sensing protein kinase AMPK. This novel insight into the cytopathological mechanisms of mitochondrial dysfunction suggests new possibilities for therapeutic intervention in mitochondrial and neurodegenerative diseases.
Barth
Christian
C
Department of Microbiology, La Trobe University, Melbourne VIC 3086, Australia.
Le
Phuong
P
Fisher
Paul R
PR
D000818:Animals; D002468:Cell Physiological Phenomena; D004023:Dictyostelium / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*
D024101:Mitochondrial Proteins