Mitochondria: more than just a powerhouse

Pioneering biochemical studies have long forged the concept that the mitochondria are the 'energy powerhouse of the cell'. These studies, combined with the unique evolutionary origin of the mitochondria, led the way to decades of research focusing on the organelle as an essential, yet independent, functional component of the cell. Recently, however, our conceptual view of this isolated organelle has been profoundly altered with the discovery that mitochondria function within an integrated reticulum that is continually remodeled by both fusion and fission events. The identification of a number of proteins that regulate these activities is beginning to provide mechanistic details of mitochondrial membrane remodeling. However, the broader question remains regarding the underlying purpose of mitochondrial dynamics and the translation of these morphological transitions into altered functional output. One hypothesis has been that mitochondrial respiration and metabolism may be spatially and temporally regulated by the architecture and positioning of the organelle. Recent evidence supports and expands this idea by demonstrating that mitochondria are an integral part of multiple cell signaling cascades. Interestingly, proteins such as GTPases, kinases and phosphatases are involved in bi-directional communication between the mitochondrial reticulum and the rest of the cell. These proteins link mitochondrial function and dynamics to the regulation of metabolism, cell-cycle control, development, antiviral responses and cell death. In this review we will highlight the emerging evidence that provides molecular definition to mitochondria as a central platform in the execution of diverse cellular events.     

Lipolysis: more than just a lipase

Successful adaptation to starvation in mammals depends heavily on the regulated mobilization of fatty acids from triacylglycerols stored in adipose tissue. Although it has long been recognized that cyclic AMP represents the critical second messenger and hormone-sensitive lipase (HSL)**Abbreviations used in this paper: ADRP, adipocyte differentiation-related protein; HSL, hormone-sensitive lipase; PKA, protein kinase A; TAG, triacylglycerol. the rate-determining enzyme for lipolysis, simple activation of the enzyme has failed to account for the robust augmentation of fatty release in response to physiological agonists. In this issue, Sztalryd et al. (2003) provide convincing support to the notion that the subcellular compartmentalization of lipase also regulates lipolysis, and, more importantly, that proteins other than HSL are localized to the lipid droplet and are indispensable for its optimal hydrolysis.     

The thalamus is more than just a relay

The lateral geniculate nucleus and pulvinar are examples of two different types of relay: the former is a first order relay, transmitting information from a subcortical source (retina), while the latter is mostly a higher order relay, transmitting information from layer 5 of one cortical area to another cortical area. First and higher order thalamic relays can also be recognized for much of the rest of thalamus, and most of thalamus seems to be comprised of higher order relays. Higher order relays seem especially important to general corticocortical communication, and this challenges and extends the conventional view that such communication is based on direct corticocortical connections.     

Mitotic inheritance of DNA methylation: more than just copy and paste

Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our improved capacity for analyzing the global DNA methylome in mammalian cells.This review focuses on the maintenance of DNA methylation patterns during mitotic cell division.We discuss the latest discoveries of the mechanisms for the inheritance of DNA methylation as a stable epigenetic memory.We also highlight recent evidence showing the rapid turnover of DNA methylation as a dynamic gene regulatory mechanism.A body of work has shown that altered DNA methylomes are common features in aging and disease.We discuss the potential links between methylation maintenance mechanisms and diseaseassociated methylation changes.     

Spindle assembly: more than just microtubules

Do actin dynamics play an active role in mitotic spindle assembly? A new study demonstrates that cortical actin polymerization assists with the earliest phase of spindle pole migration.     

Chemokines: more than just road signs

Chemokines have long been known to orchestrate dendritic-cell migration in the body. However, recent evidence has shown that chemokines not only direct the trafficking of dendritic cells but also can regulate their maturation status. Here, we propose that this dual function of chemokines ensures that T cells and dendritic cells meet in T-cell regions of lymphoid organs and that antigen is presented in an immunologically optimal context for T-cell priming.     

The versatile stellate cell - more than just a space-filler

Most epithelia contain multiple cell types that interact to perform the roles required of the tissue. In insect epithelia, the apical plasma membrane V-ATPase dominates ion-transport models, and (as in vertebrates) is usually found in specialized intercalated cell types or regions. The Malpighian tubules of several insect Orders contain not just a mitochondrion-rich principal cell expressing high levels of V-ATPase, but a smaller, intercalated "type II", "secondary" or "stellate" cell. Recent data show that this cell type plays a key role in control of chloride and water flux across the tissue, but also may play other, still unsuspected dynamic roles.     

LuxS quorum sensing: more than just a numbers game

Quorum sensing is a process of bacterial cell-to-cell communication involving the production and detection of extracellular signaling molecules called autoinducers. Quorum sensing allows populations of bacteria to collectively control gene expression, and thus synchronize group behavior. Processes controlled by quorum sensing are typically ones that are unproductive unless many bacteria act together. Most autoinducers enable intraspecies communication; however, a recently discovered autoinducer AI-2 has been proposed to serve as a 'universal signal' for interspecies communication. Studies suggest that AI-2 encodes information in addition to specifics about cell number.     

Vitamin C deficiency: more than just a nutritional disorder

Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, only a minority of the vitamin C concentration is determined by food intake. In the presence of transition metals (iron and copper), the antiscorbutic factor shifts from an antioxidant to a pro-oxidant function. Haptoglobin (Hp) is a plasma α-2 glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger). The Hp 2-2 phenotype has a lower capacity to inhibit oxidation and vitamin C depletion. In this article, two consequences of this major finding are tackled. The Hp polymorphism is an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency and scurvy, which may explain the success of long-range human migration by the natural selection of some populations characterized by high Hp 1 allele frequencies. Moreover, we propose tailoring the recommended dietary allowance (RDA) values of vitamin C, taking into consideration the Hp phenotype dependency.     

Epithelial polarity in flies: more than just crumbs

The plasma membrane of polarized epithelial cells is composed of different domains, which are associated with specific protein complexes. Recent studies in Drosophila shed new light on the functional interactions of these protein complexes during epithelial differentiation in embryogenesis.