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The Subramani Lab studies organelle homeostasis, using peroxisomes as a model, and its relevance to human disease. Over more than 35 years, the lab has helped define peroxisomal targeting signals, protein-import pathways, quality-control mechanisms, as well as proteins and mechanisms of peroxisome biogenesis and selective peroxisome turnover by pexophagy. Current work focuses on how peroxisomes arise de novo from the endoplasmic reticulum (ER) and how peroxisomes respond to proteotoxic and other abiotic stresses.
Current research
Recent work shows that protein-misfolding stress in the ER or cytosol can increase peroxisome abundance, primarily by stimulating de novo biogenesis and, to a lesser extent, growth and division. In yeast, this response can be triggered by loss of Kar2 function, tunicamycin, or DTT. The response does not require the classical unfolded protein response (UPR) regulators Ire1, Hac1, or Gcn4, and instead involves activation of heat-shock signaling and inhibition of TOR signaling. The response is conserved from yeast to human cells, and peroxisome biogenesis contributes to survival during proteotoxic stress.
Research highlights
- Peroxisomal targeting signals – discovery and evolutionary conservation of PTS1 and PTS2 pathways for matrix-protein targeting and the mPTS pathway for peroxisomal membrane protein targeting.
- Protein import and quality control – targeting-signal receptors, membrane-protein targeting, receptor recycling, and quality-control mechanisms.
- De novo peroxisome biogenesis – ER sorting, vesicle budding, and pathways that generate new peroxisomes.
- Pexophagy – selective autophagy pathways that remove peroxisomes and cytosolic pools of peroxisomal proteins.
Explore the lab
- Research – current questions and major research themes.
- Publications – listed under Research by milestones and selected publications and also chronologically under Publications tab.
- Contact – lab email and phone.