Sorting pathways of mitochondrial inner membrane proteins

Two distinct pathways of sorting and assembly of nuclear-encoded mitochondrial inner membrane proteins are described. In the first pathway, precursor proteins that carry amino-terminal targeting signals are initially translocated via contact sites between both mitochondrial membranes into the mitochondrial matrix. They become proteolytically processed, interact with the 60-kDa heat-shock protein hsp60 in the matrix and are retranslocated to the inner membrane. The sorting of subunit 9 of Neurospora crassa F0-ATPase has been studied as an example. F0 subunit 9 belongs to that class of nuclear-encoded mitochondrial proteins which are evolutionarily derived from a prokaryotic ancestor according to the endosymbiont hypothesis. We suggest that after import into mitochondria, these proteins follow the ancestral sorting and assembly pathways established in prokaryotes (conservative sorting). On the other hand, ADP/ATP carrier was found not to require interaction with hsp60 for import and assembly. This agrees with previous findings that the ADP/ATP carrier possesses non-amino-terminal targeting signals and uses a different import receptor to other mitochondrial precursor proteins. It is proposed that the ADP/ATP carrier represents a class of mitochondrial inner membrane proteins which do not have a prokaryotic equivalent and thus appear to follow a non-conservative sorting pathway.     

Sorting and assembly of mitochondrial outer membrane proteins

In the last years the picture of protein import into the mitochondria has become much more complicated in terms of new components and new sorting pathways. These novel findings have also changed views concerning the biogenesis pathway of mitochondrial outer membrane proteins. In addition to proteins anchored with transmembrane alpha-helices, the endosymbiotic origin of the mitochondria has resulted in the presence of transmembrane beta-barrels in this compartment. The sorting and assembly pathway of outer membrane proteins involves three machineries: the translocase of the outer membrane (TOM complex) the sorting and assembly machinery (SAM complex) and the MDM complex (mitochondrial distribution and morphology). Here we review recent developments on the biogenesis pathways of outer membrane proteins with a focus on Tom proteins, the most intensively studied class of these precursor proteins.     

Sorting out sound

Speech analysis is a prototypical categorical mechanism that has been examined behaviorally in work going back to Haskins Laboratory studies in the 1950s: such work examined the perception of continua between phonemes and demonstrated sharp discontinuities consistent with categorical perception. In this issue of Neuron, Raizada and Poldrack examine analysis mechanisms for such processing by measurement of the fMRI BOLD response in the boundary region between different phonemes and argue for a specific amplification mechanism for this type of categorical perception.     

Sorting out Toll signals

Upon recognition of microbial products, Toll-like receptors (TLRs) recruit distinct combinations of adaptors to induce TLR-specific gene expression. In this issue, Kagan and Medzhitov (2006) demonstrate that the adaptor TIRAP/Mal localizes to the plasma membrane by binding to phosphatidylinositol 4,5-bisphosphate (PIP2). This binding recruits a key adaptor MyD88 to TLR4, suggesting that there is crosstalk between the TLR signaling pathway and phospholipid metabolism.     

Sorting out small RNAs

Small RNAs carry out their functions by guiding Argonaute (AGO) proteins to their targets. Diverse types of small RNAs and multiple AGO proteins exist in most eukaryotic species, but how small RNAs are sorted into specific AGO complexes remains unclear. Two papers in this issue (Mi et al., 2008; Montgomery et al., 2008) now reveal the importance of the 5' terminal nucleotide of the small RNA in the sorting process in Arabidopsis.     

Sorting GPI-anchored proteins

The study of glycosylphosphatidylinositol-anchored-protein sorting has led to some surprising new findings and concepts. Evidence is accumulating that, during their delivery to the surface, different types of plasma membrane protein might be sorted from each other early in this pathway, in the endoplasmic reticulum. Furthermore, membrane-lipid composition and microdomains might have a role in the process of protein sorting in both the secretory and endocytic pathways.     

Sorting out signals in fly endosomes

Ligands and receptors that mediate cell–cell interactions during development are removed from the cell surface by endocytosis. Subsequently, many of these internalized proteins are detected in multivesicular bodies (MVBs). Recent work in different organisms has elucidated some aspects of MVB biogenesis and trafficking. This review discusses some intriguing links between these findings, the sorting of proteins in endocytic trafficking, and the regulation of signaling pathways in Drosophila .     

Sorting out bacterial viability with optical tweezers

We have developed a method, using laser, optical tweezers and direct microscopic analysis of reproductive potential and membrane integrity, to assess single-cell viability in a stationary-phase Escherichia coli population. It is demonstrated here that a reduction in cell integrity, determined by using the fluorescent nucleic acid stain propidium iodide, correlated well with a reduction in cell proliferating potential during the stationary-phase period studied. Moreover, the same cells that exhibited reduced integrity were found to be the ones that failed to divide upon nutrient addition. A small but significant number of the intact cells (496 of 7,466 [6.6%]) failed to replicate. In other words, we did not find evidence for the existence of a large population of intact but nonculturable cells during the stationary-phase period studied but it is clear that reproductive ability can be lost prior to the loss of membrane integrity. In addition, about 1% of the stationary-phase cells were able to divide only once upon nutrient addition, and in a few cases, only one of the two cells produced by division was able to divide a second time, indicating that localized cell deterioration, inherited by only one of the daughters, may occur. The usefulness of the optical trapping methodology in elucidating the mechanisms involved in stationary-phase-induced bacterial death and population heterogeneity is discussed.