Metabolism‐lipid droplet‐nucleic acid crosstalk to regulate lipid storage and other cellular processes in oleaginous Rhodococcus bacteria

Actinobacteria belonging to Mycobacterium and Rhodococcus genera are able to synthesize and intracellularly accumulate variable amounts of triacylglycerols (TAG) in the form of lipid droplets (LDs). The lipid storage capacity of LDs in cells is controlled by the balance between lipogenesis and lipolysis. The growth of LDs in bacterial cells may be directly promoted by TAG biosynthesis, whereas TAG degradation might result in the reduction of LD sizes and lipid storage capacity. Therefore, LD formation and turnover have to be precisely regulated to maintain a balanced lipid distribution, coupling gene regulation with the metabolic state of the cell. In eukaryotic cells, LDs have emerged as critical mediators of diverse cellular responses, including fatty acid trafficking and modulation of transcriptional programs. Recent studies performed in mycobacteria and rhodococci suggested the existence of similar crosstalk mechanisms between lipid metabolism, LDs, and gene expression regulation in cells. This review connects and organizes results of different studies in a comprehensive framework for providing evidence of “lipid metabolism‐LDs‐genomic DNA” crosstalk occurring in TAG‐accumulating actinobacteria. We provide examples indicating that bacterial cells evolved sensing mechanisms that detect lipid metabolites changes as indicators of metabolic states, and adapt their transcriptional profiles through epigenetic‐like mechanisms mediated by LD‐associated proteins. Here, we describe the molecular interconnections of this coupling system and the main role of each component that integrates the information about the cellular metabolic state into the regulation of lipogenesis, LD formation and transcription in oleaginous bacteria.