Biology subjects

Ukey, R.

Publications and source records attributed to Ukey, R..

2 recordsLinked to original sources

bioRxiv2026

The phage shock protein A (PspA) maintains membrane potential and supports NADH dehydrogenase function in mycobacteria

Maintenance of membrane integrity and proton motive force (PMF) is critical for bacterial survival. The phage shock protein (Psp) system, conserved across bacterial species, stabilizes the membrane, maintains PMF, and protects against envelope damage. However, how the conserved effector PspA contributes to PMF maintenance remains unclear. Here, using the mycobacterial Psp system as a genetically tractable model, we provide mechanistic insight into this process. We show that PspA and the accessory protein PspM jointly sustain membrane potential, with PspM required to maintain a ~70 kDa PspA isoform at the membrane during envelope stress. Loss of PspA increases susceptibility to thioridazine, which targets type II NADH dehydrogenase (NDH-2), and to Ro 48-8071, an inhibitor of menaquinone biosynthesis. Notably, hypersusceptibility to thioridazine is rescued by exogenous menaquinone. Consistent with these phenotypes, a pspA-deficient mutant exhibits impaired NADH dehydrogenase activity despite unchanged abundance of NDH-2 and menaquinone (MK-9). Together, these findings identify a functional link between PspA and NADH dehydrogenase-dependent respiration and suggest that PspA contributes to PMF maintenance by supporting respiratory electron transfer.

molecular biology↗

bioRxiv2023

Heterogeneity of foam cell biogenesis across diseases

Foam cells are dysfunctional, lipid-laden macrophages associated with chronic inflammation of diverse origin. The long-standing paradigm that foam cells are cholesterol-laden derives from atherosclerosis research. We previously showed that, in tuberculosis, foam cells surprisingly accumulate triglycerides. Here, we utilized bacterial (Mycobacterium tuberculosis), fungal (Cryptococcus neoformans), and human papillary renal cell carcinoma (pRCC) models to address the need for a new explanation of foam cell biogenesis. We applied mass spectrometry-based imaging to assess the spatial distribution of storage lipids relative to foam-cell-rich areas in lesional tissues, and we characterized lipid-laden macrophages generated under corresponding in vitro conditions. The in vivo data and the in vitro findings showed that cryptococcus-infected macrophages accumulate triglycerides, while macrophages exposed to pRCC- conditioned-medium accumulated both triglycerides and cholesterol. Moreover, cryptococcus- and mycobacterium-infected macrophages accumulated triglycerides in different ways. Collectively, the data show that the molecular events underlying foam cell formation are specific to disease and microenvironment. Since foam cells are potential therapeutic targets, recognizing that their formation is disease-specific opens new biomedical research directions.

immunology↗