Post Genomics Identification of Blood Stage Invasins of Plasmodium Falciparum

Abstract

Human mitochondria require ~1500 proteins for its constitutive functions. However, the mitochondrial genome is gene deficient and most of the mitochondrial proteome is nuclear encoded and transported into the organelle. Import of majority of mitochondrial proteome is mediated by presequence pathway and requires functional interplay between a subset of molecular chaperones, along with accessory factors. Although detailed analysis has been carried out in yeast system, our understanding of human mitochondrial proteome maintenance has been severely limited by the absence of significant structural and functional information on the organization TIM23 complex in humans. Recent studies have revealed the presence of multiple presequence translocases in human mitochondria that show considerable diversity in their substrate and physiological specificity. The core organization and inter-molecular interactions between these machineries seems to be evolutionary conserved. These translocases have principally diversified due to divergence of Hsp70 co-chaperones and channel component Tim17. Another important feature associated with human mitochondrial translocases, which in most cases are absent in lower eukaryotes, is its multifunctionality. Other than housekeeping protein import, human mitochondrial translocases have gained secondary functions such asinvolvment in ROS sensing and regulation of redox balance, modulation of cellular sensitivity to xenobiotic drugs, maintenance of mitochondrial DNA, assembly of respiratory complexes' and import of non-canonical mitochondrial substrates. The origin of multifunctionality is indicative towards the possibility of functional connections between mitochondrial protein import and regulation of cellular pathways; hence, opening up new avenues of future research. Keywords IntroductionMitochondria are endosymbiotic cellular organelle enclosed in double membrane and form an integral part of eukaryotic cells. The word mitochondrion comes from the Greek ìßôïò, mitos, i.e. "thread", and ÷ïíäñßïí, chondrion, i.e. "granule". The term "mitochondria" was coined by Carl Benda in 1898 (cited in Margulis, 1970). Benjamin F. Kingsbury (1912) first related these organelles with cell respiration (cited in Sagan, 1967), followed by Otto Heinrich Warburg (Ernster and Schatz, 1981; Gray et al., 1999). In addition to supplying cellular energy, mitochondria are involved in other tasks such as signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth (Gray et al., 1999). Mitochondria have been implicated in several human diseases, including mitochondrial disorders and cardiac dysfunction, and may play a role in the aging process (Fulda et al., 2010; Gulbins et al., 2003; Hayashi et al., 2009; Kroemer, 2006; Lesnefsky et al., 2001; McBride et al., 2006).Mitochondrial genomes are very small and show a great deal of variation as a result of divergent evolution (Ernster and Schatz, 1981; Henze and Martin, 2003; Peng et al., 2005). The human mitochondrial geno...