Lipid droplets (LDs) make physical contacts with various organelles in eukaryotic cells including mitochondria. The existence of these contacts is well-known but poorly described. Here, we review recent advances in the understanding of the physical and functional links between LDs and mitochondria, and their implications in fatty acid transfer, cell signaling, and various diseases.

Our body stores energy mostly in form of fatty acids (FAs) in lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes and mitochondria. This transfer is dependent on close opposition of LDs and mitochondria and peroxisomes and happens at membrane contact sites. However, the composition and the dynamics of these contact sites is not well understood, which is in part due to the dependence on the metabolic state of the cell and on the cell- and tissue-type. Here, we summarize the current knowledge on the contacts between lipid droplets and mitochondria both in mammals and in the yeast Saccharomyces cerevisiae, in which various contact sites are well studied. We discuss possible functions of the contact site and their implication in disease.

Lipid droplets (LDs) are important for the storage of energy and lipid components. The perilipin family in mammals includes five proteins (PLIN1 to PLIN5), all of which are abundant on the surface of LDs in different tissues and play a role in LD stability and degradation by lipases. We discuss how perilipins interact with LDs, their function, and their implication in metabolic disease.

Perilipins are abundant lipid droplet (LD) proteins present in all metazoans and also in Amoebozoa and fungi. Humans express five perilipins, which share a similar domain organization: an amino-terminal PAT domain and an 11-mer repeat region, which can fold into amphipathic helices that interact with LDs, followed by a structured carboxy-terminal domain. Variations of this organization that arose during vertebrate evolution allow for functional specialization between perilipins in relation to the metabolic needs of different tissues. We discuss how different features of perilipins influence their interaction with LDs and their cellular targeting. PLIN1 and PLIN5 play a direct role in lipolysis by regulating the recruitment of lipases to LDs and LD interaction with mitochondria. Other perilipins, particularly PLIN2, appear to protect LDs from lipolysis, but the molecular mechanism is not clear. PLIN4 stands out with its long repetitive region, whereas PLIN3 is most widely expressed and is used as a nascent LD marker. Finally, we discuss the genetic variability in perilipins in connection with metabolic disease, prominent for PLIN1 and PLIN4, underlying the importance of understanding the molecular function of perilipins.

This review focuses on deciphering the redox and metabolic profiles of breast cancer and associated adipose tissue as a part of a unique Warburg pseudo-organ. In the light of the coupled cancer and adipose tissue redox-metabolic reprogramming, mechanistic links to estrogen receptors, tumor microenvironment cell heterogeneity, inflammation, and circadian rhythms as important players affecting breast cancer development, progression, and prognosis are also discussed (Created with BioRender.com).

Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.

Nuclear lamins, constituents of the nuclear lamina, bridge the gap between the nuclear membranes and chromatin. Here we discuss the lamins’ structure, assembly dynamics and their interactions with chromatin. We focus on the mechanical roles of lamins, from molecular to network scales, and finalize by linking the structural, mechanical, and molecular properties of lamins with biological function and disease.

Nuclear lamins are type-V intermediate filaments that are involved in many nuclear processes. In mammals, A- and B-type lamins assemble into separate physical meshwork underneath the inner nuclear membrane, the nuclear lamina, with some residual fraction localized within the nucleoplasm. Lamins are the major part of the nucleoskeleton, providing mechanical strength and flexibility to protect the genome and allow nuclear deformability, whilst also contributing to gene regulation via interactions with chromatin. While lamins are the evolutionary ancestors of all intermediate filament family proteins, their ultimate filamentous assembly is markedly different from their cytoplasmic counterparts. Interestingly, hundreds of genetic mutations in the lamina proteins have been causally linked with a broad range of human pathologies, termed laminopathies. These include muscular, neurological and metabolic disorders, as well as premature aging diseases. Recent technological advances have contributed to resolving the filamentous structure of lamins and the corresponding lamina organization. In this review we revisit the multiscale lamin organization and discuss its implications on nuclear mechanics and chromatin organization within lamina associated domains.

Living organisms experience diverse external environments throughout life; one common situation is nutrient limitation. To survive nutrient stress, eukaryotic cells utilize macroautophagy/autophagy. During autophagy, cells remove unwanted material by packaging them within double-membraned autophagosomes and delivering the cargo to vacuoles for degradation. Here, we summarize different nutrient contexts and signaling pathways that regulate autophagy, specifically in Saccharomyces cerevisiae.

Macroautophagy/autophagy is a highly conserved catabolic process vital for cellular stress responses and maintaining equilibrium within the cell. Malfunctioning autophagy has been implicated in the pathogenesis of various diseases, including certain neurodegenerative disorders, diabetes, metabolic diseases, and cancer. Cells face diverse metabolic challenges, such as limitations in nitrogen, carbon, and minerals such as phosphate and iron, necessitating the integration of complex metabolic information. Cells utilize a signal transduction network of sensors, transducers, and effectors to coordinate the execution of the autophagic response, concomitant with the severity of the nutrient-starvation condition. This review presents the current mechanistic understanding of how cells regulate the initiation of autophagy through various nutrient-dependent signaling pathways. Emphasizing findings from studies in yeast, we explore the emerging principles that underlie the nutrient-dependent regulation of autophagy, significantly shaping stress-induced autophagy responses under various metabolic stress conditions.