Biology subjects

Raghuram, N.

Publications and source records attributed to Raghuram, N..

3 recordsLinked to original sources

bioRxiv2025

Alterations in Lipid Saturation Trigger Remodeling of the Outer Mitochondrial Membrane

Lipid saturation is a key determinant of membrane function and organelle health, with changes in saturation triggering adaptive quality control mechanisms to maintain membrane integrity. Among cellular membranes, the mitochondrial outer membrane (OMM) is an important interface for many cellular functions, but how lipid saturation impacts OMM function remains unclear. Here, we show that increased intracellular unsaturated fatty acids (UFAs) remodel the OMM by promoting the formation of multilamellar mitochondrial-derived compartments (MDCs), which sequester proteins and lipids from the OMM. These effects depend on the incorporation of UFAs into membrane phospholipids, suggesting that changes in membrane bilayer composition mediate this process. Furthermore, elevated UFAs impair the assembly of the OMM protein translocase (TOM) complex, with unassembled TOM components captured into MDCs. Collectively, these findings suggest that alterations in phospholipid saturation may destabilize OMM protein complexes and trigger an adaptive response to sequester excess membrane proteins through MDC formation. Significance StatementO_LIMitochondrial-derived compartments are multilamellar structures that sequester protein and lipids of the outer mitochondrial membrane in response to metabolic and membrane perturbations, but it is largely unknown how membrane fluidity influences this pathway. C_LIO_LIIncreased levels of unsaturated phospholipids may disrupt the TOM complex, a large multi-subunit complex on the outer mitochondrial membrane, to promote the formation of mitochondrial-derived compartments, while increased levels of saturated phospholipids inhibits formation of mitochondrial-derived compartments. C_LIO_LIThese findings reveal a link between phospholipid composition and protein stress in driving mitochondrial-derived compartment biogenesis, and thus mitochondrial quality control. C_LI

cell biology↗

bioRxiv2024

Amino acids trigger MDC-dependent mitochondrial remodeling by altering mitochondrial function

Cells utilize numerous pathways to maintain mitochondrial homeostasis, including a recently identified mechanism that adjusts the content of the outer mitochondrial membrane (OMM) through formation of OMM-derived multilamellar domains called mitochondrial-derived compartments, or MDCs. MDCs are triggered by perturbations in mitochondrial lipid and protein content, as well as increases in intracellular amino acids. Here, we sought to understand how amino acids trigger MDCs. We show that amino acid-activation of MDCs is dependent on the functional state of mitochondria. While amino acid excess triggers MDC formation when cells are grown on fermentable carbon sources, stimulating mitochondrial biogenesis blocks MDC formation. Moreover, amino acid elevation depletes TCA cycle metabolites in yeast, and preventing consumption of TCA cycle intermediates for amino acid catabolism suppresses MDC formation. Finally, we show that directly impairing the TCA cycle is sufficient to trigger MDC formation in the absence of amino acid stress. These results demonstrate that amino acids stimulate MDC formation by perturbing mitochondrial metabolism. SUMMARYRaghuram and Hughes uncover a mechanism by which amino acids promote mitochondrial membrane remodeling via the Mitochondrial Derived Compartment (MDC) pathway. They show that elevated amino acids trigger MDC formation through a depletion of TCA cycle metabolites.

cell biology↗

bioRxiv2022

Genomewide basis for nitrogen use efficiency in contrasting genotypes of rice

Rice is an ideal crop with huge germplasm diversity and post-genomic resources for improvement of nitrogen (N) use efficiency (NUE). There is a paucity of comparative studies on rice genotypes contrasting for NUE, especially with urea, the predominant fertilizer in rice growing countries. In this study, low urea-responsive transcriptomes of contrasting rice genotypes namely Nidhi (low NUE) and Panvel1 (high NUE) were compared. They were based on whole plants grown for 21 days in pots containing nutrient-depleted soil fertilized with normal (15 mM) and low urea (1.5 mM) media. There were 1497 and 2819 differentially expressed genes (DEGs) in Nidhi and Panvel1, respectively, of which 271 were common. Though 1226 DEGs were genotype-specific in Nidhi and 2548 in Panvel1, there was far higher commonality in underlying processes. High NUE is associated with the urea-responsive regulation of other nutrient transporters, miRNAs, transcription factors and better photosynthesis, water use efficiency and post translational modifications. Many of their genes co-localized to NUE QTLs on chromosomes 1, 3 and 9. Field evaluation of the contrasting genotypes under different doses of urea revealed better performance of Panvel1 in different agronomic parameters including grain yield, transport/uptake efficiencies and NUE. Comparison of our urea-based transcriptomes with our previous nitrate-based transcriptomes from the same contrasting rice genotypes revealed many common processes despite large differences in their expression profiles. Our model proposes that differential involvement of transporters and transcription factors among others contributes to better urea uptake, translocation, utilization, flower development and yield for high NUE. SummaryRice genotypes with contrasting urea use efficiency differ in the role of transporters, transcription factors, miRNAs, post-translational modifications, photosynthesis and water use efficiency

plant biology↗