MI64CH22-Johnson ARI 5 August 2010 18:59 Mitochondrion-Related Organelles in Eukaryotic Protists April M. Shiflett and Patricia J. Johnson Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California 90095-1489; email: [email protected] Annu. Rev. Microbiol. 2010. 64:409–29 Key Words First published online as a Review in Advance on hydrogenosome, mitosome, evolution, microaerophilic protists, June 9, 2010 biogenesis The Annual Review of Microbiology is online at micro.annualreviews.org Abstract This article’s doi: The discovery of mitochondrion-type genes in organisms thought to 10.1146/annurev.micro.62.081307.162826 lack mitochondria led to the demonstration that hydrogenosomes share Copyright c 2010 by Annual Reviews. a common ancestry with mitochondria, as well as the discovery of mi- All rights reserved by University of Massachusetts - Amherst on 02/02/12. For personal use only. tosomes in multiple eukaryotic lineages. No examples of examined eu- 0066-4227/10/1013-0409$20.00 Annu. Rev. Microbiol. 2010.64:409-429. Downloaded from www.annualreviews.org karyotes lacking a mitochondrion-related organelle exist, implying that the endosymbiont that gave rise to the mitochondrion was present in the first eukaryote. These organelles, known as hydrogenosomes, mi- tosomes, or mitochondrion-like organelles, are typically reduced, both structurally and biochemically, relative to classical mitochondria. How- ever, despite their diversification and adaptation to different niches, all appear to play a role in Fe-S cluster assembly, as observed for mitochon- dria. Although evidence supports the use of common protein targeting mechanisms in the biogenesis of these diverse organelles, divergent fea- tures are also apparent. This review examines the metabolism and bio- genesis of these organelles in divergent unicellular microbes, with a focus on parasitic protists. 409 MI64CH22-Johnson ARI 5 August 2010 18:59 features, eukaryotes are more complex and ex- Contents hibit several distinctive physical characteris- tics absent in archaea and eubacteria. These INTRODUCTION.................. 410 characteristics include an extensive endomem- HYDROGENOSOMES.............. 411 brane system and the compartmentalization of PHYLOGENETIC EVIDENCE OF metabolic pathways into discrete membrane- PRIMITIVE MITOCHONDRIAL bound organelles; one such organelle is the ANCESTRY: THE mitochondrion. How eukaryotic cells evolved CHAPERONIN STORY . 413 these distinctive features and how these features BIOCHEMICAL ACTIVITIES: IT’S have diversified during the radiation of evolu- NOTJUSTABOUTATP......... 414 tionarily distinct lineages remain the focus of AN INTERMEDIATE much research (8). The acquisition of the mi- ORGANELLE IN BLASTOCYSTIS tochondrion during eukaryotic evolution may SPECIES......................... 417 have been a central catalyst allowing further PROTEIN TARGETING IN development of the many unique features of HYDROGENOSOMES AND eukaryotic cells. MITOSOMES.................... 417 The mitochondrion was originally hypoth- N-Terminal Presequences. 418 esized by Margulis and colleagues (75) to be the Mitochondrial Carrier Family result of endosymbiosis. The ancient eukary- Proteins........................ 421 otic forerunner was proposed to have engulfed Unclassified Membrane Proteins. 422 a bacterium, which was retained and eventually CONCLUSIONS AND degenerated to the point of being dependent REMAINING QUESTIONS . 422 on the host cell. Much evidence now supports the basic tenets of this theory, including the presence of a double membrane containing a unique bacterial lipid called cardiolipin present INTRODUCTION only on the inner membrane of the organelle. Deciphering the origins of eukaryotic cells The sequencing of several mitochondrial is one of the more challenging problems in genomes and subsequent phylogenetic analyses evolutionary biology today. The seminal work led to the conclusion that the mitochondrial of Woese et al. (122) led to the grouping of endosymbiont was closely related to modern all living organisms into three domains of life: Alphaproteobacteria (123), with its closest eubacteria, archaea (or archaebacteria), and existing relative being Rickettsia (4). This eukaryotes. Over the past 15 years, extensive answered the question of who donated the Mitochondrion: by University of Massachusetts - Amherst on 02/02/12. For personal use only. sequencing of the genomes of organisms from endosymbiont; but what about the host cell? a membrane-bound Annu. Rev. Microbiol. 2010.64:409-429. Downloaded from www.annualreviews.org organelle in eukaryotic all three domains has revealed that eukaryotic Multiple arguments have been presented cells that produces genomes contain both eubacterial and archaeal and continue to be discussed regarding the bio- ATP via oxidative contributions (35, 96). Information genes logical nature of the cell that engulfed the pro- phosphorylation, in encoding proteins involved in processes such tomitochondrion (77). One view posits that the addition to housing as translation, transcription, and replication protoeukaryote was a member of the archaea various other metabolic pathways appear to be homologous to archaeal genes. and that acquisition of the mitochondrial en- Eubacterial contributions to the eukaryotic dosymbiont led to rapid development of the Endosymbiont: an organism that lives genome are seen primarily in the so-called accompanying features that now define eukary- inside the cells of operational genes, which encode proteins such otes. Another theory states that many of these another organism (the as metabolic enzymes, structural proteins, and eukaryotic features were already in place, i.e., host) and causes no membrane components (124). that such subcellular structures as the endo- harm and is often Although many core metabolic properties plasmic reticulum (ER) and nucleus were likely beneficial of eukaryotes have archaeal and eubacterial already present in the protoeukaryote, making 410 Shiflett · Johnson MI64CH22-Johnson ARI 5 August 2010 18:59 alteration of the endosymbiont into a bona fide amitochondriates. Moreover, these organisms organelle a more easily explainable process (33). contain highly modified, or even relic, or- Key to distinguishing between these compet- ganelles that are thought to be derived from Microsporidia: ing hypotheses is determining when the mito- the protomitochondrion: a hydrogenosome, a spore-forming chondrion was acquired. Various theories have mitosome, and a mitochondrion-like organelle unicellular fungal been proposed to explain the circumstances sur- (MLO) (Figure 1). parasites that live an rounding both the acquisition and retention of T. vaginalis and G. lamblia have served obligate intracellular the mitochondrion. Many of these theories ex- as model organisms for the study of hy- lifestyle and exhibit extreme reductive cell pound in particular upon the nature of the host drogenosomes and mitosomes, respectively (27, biology and invoke one or more endosymbiotic events 107). Hydrogenosomes produce ATP through LBA: long branch to account for specific traits present in the pro- substrate-level phosphorylation, creating hy- attraction toeukaryotic cell. Several of these hypotheses drogen as a by-product (69). Mitosomes do not Hydrogenosome: an have been described in detail (28, 72, 78, 81) and produce ATP, and until recently their poten- organelle are reviewed extensively by Martin et al. (77). tial metabolic role in the cell was somewhat of a evolutionarily related Early constructions of the eukaryotic tree of mystery (114). Despite differences in metabolic to mitochondria that life led to the formation of the Archezoan hy- functions, the majority of the data currently produces ATP via pothesis (16, 103). These phylogenies, which available support a single endosymbiosis that substrate-level phosphorylation and were based on both rRNA and elongation factor gave rise to mitochondria and resulted in the molecular hydrogen (EF) protein sequences, placed three highly di- presence of hydrogenosomes or mitosomes in Mitosome: vergent branches containing Trichomonas vagi- a variety of protists. The vast differences ob- an organelle nalis, Giardia lamblia, and microsporidia at the served in these organelles would then be the evolutionarily related base of the tree (103). Each of these organ- result of divergent evolution in highly special- to mitochondria that isms appeared to have arisen prior to the acqui- ized ecological niches. Although descent from a does not produce ATP sition of mitochondria, and it was speculated single, common, protomitochondrial endosym- or hydrogen and appears to lack most that they represented primitively amitochon- biont has been the prevailing view for sev- other metabolic driate eukaryotic cells. This would imply that eral years, distinguished scientists continue to pathways associated the characteristic features of a eukaryotic cell raise important arguments contrary to this view with either such as a nucleus and flagella predated the mi- (22, 76). mitochondria or tochondrial endosymbiosis. The study of such hydrogenosomes organisms would consequently aid in resolving the conundrum of protoeukaryotic identity. HYDROGENOSOMES The first indication that these organisms Hydrogenosomes were first described in tri- were not true archezoans came from studies of chomonads by Lindmark & Muller following the microsporidia. Analysis of additional genes futile attempts to detect mitochondrial and per- by University of Massachusetts