Energy deprivation is a frequent adverse event in tumors that is caused by mutations, malperfusion, hypoxia, and nutrition deficit. The resulting bioenergetic stress leads to signaling and metabolic adaptation responses in tumor cells, secures survival, and adjusts migration activity. The kinetic responses of cancer cells to energy deficit were recently identified, including a switch of invasive cancer cells to energy-conservative amoeboid migration and an enhanced capability for distant metastasis. We review the energy programs employed by different cancer invasion modes including collective, mesenchymal, and amoeboid migration, as well as their interconversion in response to energy deprivation, and we discuss the consequences for metastatic escape. Understanding the energy requirements of amoeboid and other dissemination strategies offers rationales for improving therapeutic targeting of metastatic cancer progression.

Brown adipose tissue (BAT) controls mammalian core body temperature by non-shivering thermogenesis. BAT is extraordinarily rich in mitochondria, which have the peculiarity of generating heat by uncoupled respiration. Since the mitochondrial activity of BAT is subject to cycles of activation and deactivation in response to environmental temperature changes, an integrated mitochondrial quality control (MQC) system is of fundamental importance to ensure BAT physiology. Here, we provide an overview of the conventional and alternative mechanisms through which thermogenic adipocytes selectively remove damaged parts of mitochondria and how macrophages participate in the MQC system by removing extracellular mitochondrial waste to maintain the thermogenic function of BAT.

The existence of stem cells (SCs) at the tip of the cellular differentiation hierarchy has fascinated the scientific community ever since their discovery in the early 1950s to 1960s. Despite the remarkable success of the SC theory and the development of SC-based treatments, fundamental features of SCs remain enigmatic. Recent advances in single-cell lineage tracing, live imaging, and genomic technologies have allowed capture of life histories and transcriptional signatures of individual cells, leaving SCs much less space to 'hide'. Focusing on epithelial SCs and comparing them to other SCs, we discuss new paradigms of the SC niche, dynamics, and pathology, highlighting key open questions in SC biology that need to be resolved for harnessing SC potential in regenerative medicine.

An increasing corpus of research has demonstrated that membrane shape, generated either by the external environment of the cell or by intrinsic mechanisms such as cytokinesis and vesicle or organelle formation, is an important parameter in the control of diverse cellular processes. In this review we discuss recent findings that demonstrate how membrane curvature (from nanometer to micron length-scales) alters protein function. We describe an expanding toolkit for experimentally modulating membrane curvature to reveal effects on protein function, and discuss how membrane curvature - far from being a passive consequence of the physical environment and the internal protein activity of a cell - is an important signal that controls protein affinity and enzymatic activity to ensure robust forward progression of key processes within the cell.

Loss-of-function heterozygous mutations in GRN, the gene encoding progranulin (PGRN), were identified in patients with frontotemporal lobar degeneration (FTLD) almost two decades ago and are generally linked to reduced PGRN protein expression levels. Although initial characterization of PGRN function primarily focused on its role in extracellular signaling as a secreted protein, more recent studies revealed critical roles of PGRN in regulating lysosome function, including proteolysis and lipid degradation, consistent with its lysosomal localization. Emerging from these studies is the notion that PGRN regulates glucocerebrosidase activity via direct chaperone activities and via interaction with prosaposin (i.e., a key regulator of lysosomal sphingolipid-metabolizing enzymes), as well as with the anionic phospholipid bis(monoacylglycero)phosphate. This emerging lysosomal biology of PGRN identified novel and promising opportunities in therapeutic discovery as well as biomarker development.

Olfactory receptors (ORs) are widely expressed in extra-nasal tissues, where they participate in the regulation of divergent physiological processes. An increasing body of evidence over the past decade has revealed important regulatory roles for extra-nasal ORs in glucose metabolism. Recently, nonodorant endogenous ligands of ORs with metabolic significance have been identified, implying the therapeutic potential of ORs in the treatment of metabolic diseases, such as diabetes and obesity. In this review, we summarize current understanding of the expression patterns and functions of ORs in key tissues involved in glucose metabolism modulation, describe odorant and endogenous OR ligands, explain the biased signaling downstream of ORs, and outline OR therapeutic potential.