Some like it hot: A hypothesis for establishment of the proto-mitochondrial endosymbiont during eukaryogenesis

Available evidence suggests that two prokaryotes, an archaeon and a bacterium, collaborated in the eventual formation of nucleated cells with arguably increased complexity of form and function. However, the mechanisms by which bacteria and archaea cooperated in the formation of eukaryotes, and the selective pressures that promoted this partnership, remain a mystery. Mitochondria are eukaryotic organelles thought to be derived from respiring, alpha-proteobacterial endosymbionts capable of generating ATP by oxidative phosphorylation. The earliest eukaryote likely harbored mitochondria, since all characterized eukaryotic lineages show evidence of containing, or having once contained, these organelles. Consequently, it has been argued that mitochondria, and particularly the ATP that can be generated by these compartments, allowed for evolution toward an expanded number of proteins, an increase in overt specialization achievable by eukaryotic cells, and the eventual formation of complex multicellular organisms. However, the relationship between mitochondrial ATP generation and its potency in allowing genome expansion has been a matter of debate. Moreover, how and why an endosymbiont not yet converted to an organelle might purposefully provide ATP to its host is not clear. Here, I propose that the initial driving force for integration of the proto-mitochondrial endosymbiont within the proto-eukaryotic host may not have been provision of ATP to its archaeal partner, but rather that heat generated by the endosymbiont allowed the archaeal host to endure lower temperatures at the outset of eukaryogenesis. I discuss how this arrangement may have led to the increased apparent complexity that is characteristic of eukaryotes

Some like it hot: A hypothesis regarding establishment of the proto-mitochondrial endosymbiont during eukaryogenesis

Eukaryotic cells are generally characterized by a considerable increase in subcellular compartmentalization in comparison to prokaryotes. Eukaryotes can also form multicellular organisms consisting of highly specialized cell types. Most evidence suggests that the earliest eukaryotes consisted of mitochondria derived from an α-proteobacterial ancestor enclosed within an archaeon-derived host cell. However, what specific benefits the archaeal host and the proto-mitochondrial endosymbiont each obtained from this endosymbiotic relationship remains unclear. In this work, we argue that endosymbiont-generated heat may have initially permitted an archaeal host living at very high temperatures to colonize a cooler environment, and we describe how subsequent events could have prompted the increased apparent complexity of eukaryotic cells

Some like it hot: A hypothesis regarding establishment of the proto-mitochondrial endosymbiont during eukaryogenesis

Eukaryotic cells are generally characterized by a considerable increase in subcellular compartmentalization in comparison to prokaryotes. Eukaryotes can also form multicellular organisms consisting of highly specialized cell types. Most evidence suggests that the earliest eukaryotes consisted of mitochondria derived from an α-proteobacterial ancestor enclosed within an archaeon-derived host cell. However, what specific benefits the archaeal host and the proto-mitochondrial endosymbiont each obtained from this endosymbiotic relationship remains unclear. In this work, we argue that endosymbiont-generated heat may have initially permitted an archaeal host living at very high temperatures to colonize a cooler environment, and we describe how subsequent events could have prompted the increased apparent complexity of eukaryotic cells

Some like it hot: A hypothesis for establishment of the proto-mitochondrial endosymbiont during eukaryogenesis

Available evidence suggests that two prokaryotes, an archaeon and a bacterium, collaborated in the eventual formation of nucleated cells with arguably increased complexity of form and function. However, the mechanisms by which bacteria and archaea cooperated in the formation of eukaryotes, and the selective pressures that promoted this partnership, remain a mystery. Mitochondria are eukaryotic organelles thought to be derived from respiring, alpha-proteobacterial endosymbionts capable of generating ATP by oxidative phosphorylation. The earliest eukaryote likely harbored mitochondria, since all characterized eukaryotic lineages show evidence of containing, or having once contained, these organelles. Consequently, it has been argued that mitochondria, and particularly the ATP that can be generated by these compartments, allowed for evolution toward an expanded number of proteins, an increase in overt specialization achievable by eukaryotic cells, and the eventual formation of complex multicellular organisms. However, the relationship between mitochondrial ATP generation and its potency in allowing genome expansion has been a matter of debate. Moreover, how and why an endosymbiont not yet converted to an organelle might purposefully provide ATP to its host is not clear. Here, I propose that the initial driving force for integration of the proto-mitochondrial endosymbiont within the proto-eukaryotic host may not have been provision of ATP to its archaeal partner, but rather that heat generated by the endosymbiont allowed the archaeal host to endure lower temperatures at the outset of eukaryogenesis. I discuss how this arrangement may have led to the increased apparent complexity that is characteristic of eukaryotes

Wherever I may roam : organellar protein targeting and evolvability

Many functions of eukaryotic cells are compartmentalized within membrane-bound organelles. One or more cis-encoded signals within a polypeptide sequence typically govern protein targeting to and within destination organelles. Perhaps unexpectedly, organelle targeting does not occur with high specificity, but instead is characterized by considerable degeneracy and inefficiency. Indeed, the same peptide signals can target proteins to more than one location, randomized sequences can easily direct proteins to organelles, and many enzymes appear to traverse different subcellular settings across eukaryotic phylogeny. We discuss the potential benefits provided by flexibility in organelle targeting, with a special emphasis on horizontally transferred and de novo proteins. Moreover, we consider how these new organelle residents can be protected and maintained before they contribute to the needs of the cell and promote fitness.Peer reviewe

Modeling Adsorption, Conformation, and Orientation of the Fis1 Tail Anchor at the Mitochondrial Outer Membrane

Proteins can be targeted to organellar membranes by using a tail anchor (TA), a stretch of hydrophobic amino acids found at the polypeptide carboxyl-terminus. The Fis1 protein (Fis1p), which promotes mitochondrial and peroxisomal division in the yeast Saccharomyces cerevisiae, is targeted to those organelles by its TA. Substantial evidence suggests that Fis1p insertion into the mitochondrial outer membrane can occur without the need for a translocation machinery. However, recent findings raise the possibility that Fis1p insertion into mitochondria might be promoted by a proteinaceous complex. Here, we have performed atomistic and coarse-grained molecular dynamics simulations to analyze the adsorption, conformation, and orientation of the Fis1(TA). Our results support stable insertion at the mitochondrial outer membrane in a monotopic, rather than a bitopic (transmembrane), configuration. Once inserted in the monotopic orientation, unassisted transition to the bitopic orientation is expected to be blocked by the highly charged nature of the TA carboxyl-terminus and by the Fis1p cytosolic domain. Our results are consistent with a model in which Fis1p does not require a translocation machinery for insertion at mitochondria

Modeling Adsorption, Conformation, and Orientation of the Fis1 Tail Anchor at the Mitochondrial Outer Membrane

Proteins can be targeted to organellar membranes by using a tail anchor (TA), a stretch of hydrophobic amino acids found at the polypeptide carboxyl-terminus. The Fis1 protein (Fis1p), which promotes mitochondrial and peroxisomal division in the yeast Saccharomyces cerevisiae, is targeted to those organelles by its TA. Substantial evidence suggests that Fis1p insertion into the mitochondrial outer membrane can occur without the need for a translocation machinery. However, recent findings raise the possibility that Fis1p insertion into mitochondria might be promoted by a proteinaceous complex. Here, we have performed atomistic and coarse-grained molecular dynamics simulations to analyze the adsorption, conformation, and orientation of the Fis1(TA). Our results support stable insertion at the mitochondrial outer membrane in a monotopic, rather than a bitopic (transmembrane), configuration. Once inserted in the monotopic orientation, unassisted transition to the bitopic orientation is expected to be blocked by the highly charged nature of the TA carboxyl-terminus and by the Fis1p cytosolic domain. Our results are consistent with a model in which Fis1p does not require a translocation machinery for insertion at mitochondria

Functional Analysis of Subunit e of the F\u3csub\u3e1\u3c/sub\u3eF\u3csub\u3eo\u3c/sub\u3e-ATP Synthase of the Yeast \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e: Importance of the N-Terminal Membrane Anchor Region

Mitochondrial F1Fo-ATP synthase complexes do not exist as physically independent entities but rather form dimeric and possibly oligomeric complexes in the inner mitochondrial membrane. Stable dimerization of two F1Fo-monomeric complexes involves the physical association of two membrane-embedded Fo-sectors. Previously, formation of the ATP synthase dimeric-oligomeric network was demonstrated to play a critical role in modulating the morphology of the mitochondrial inner membrane. In Saccharomyces cerevisiae, subunit e (Su e) of the Fo-sector plays a central role in supporting ATP synthase dimerization. The Su e protein is anchored to the inner membrane via a hydrophobic region located at its N-terminal end. The hydrophilic C-terminal region of Su e resides in the intermembrane space and contains a conserved coiled-coil motif. In the present study, we focused on characterizing the importance of these regions for the function of Su e. We created a number of C-terminal-truncated derivatives of the Su e protein and expressed them in the Su e null yeast mutant. Mitochondria were isolated from the resulting transformant strains, and a number of functions of Su e were analyzed. Our results indicate that the N-terminal hydrophobic region plays important roles in the Su e-dependent processes of mitochondrial DNA maintenance, modulation of mitochondrial morphology, and stabilization of the dimer-specific Fo subunits, subunits g and k. Furthermore, we show that the C-terminal coiled-coil region of Su e functions to stabilize the dimeric form of detergent-solubilized ATP synthase complexes. Finally, we propose a model to explain how Su e supports the assembly of the ATP synthase dimers-oligomers in the mitochondrial membrane

Bacterial tail anchors can target to the mitochondrial outer membrane

Background: During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol. Results: Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM. Conclusions: Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.Peer reviewe