The Henne Lab is interested in how cells spatially organize their metabolism--and how this spatial organization enables cells and organisms to adapt to metabolic challenges. We are trying to answer three fundamental questions:
1) how are lipid droplets (major lipid storage organelles) made and organized within cells?,
2) how are lipid droplets assigned to their specific jobs in cell metabolism?, and
3) how do cells spatially organize metabolic pathways, and how do inter-organelle contact sites contribute to this?
A current focus is understanding how cells store lipids in lipid droplets (LDs), and also arrange LDs in functionally relevant patterns within cells to enable homeostasis. LDs do not work in isolation, and a key mechanism to spatially organize them is to attach them to other organelles. Recently, we characterized a protein family (the PXA domain-containing family) that plays key roles in LD organization and inter-organelle crosstalk. Budding yeast encode a PXA domain-containing protein called Mdm1 that we found acts as a "molecular tether" connecting LDs to the yeast lysosome/vacuole (Henne, JCB, 2015; Hariri, EMBO reports, 2018; Hariri, JCB, 2019). Mdm1 is highly conserved in metazoans, and we also found that its human homolog SNX14 regulates LD growth and homeostasis, which is perturbed in the genetic neurological disease SCAR20 (Bryant, HMG, 2018; Datta, JCB, 2019; Datta, PNAS, 2020). The Drosophila fruit fly also encodes a Mdm1 homolog called Snazarus (Snz), which we discovered localizes to ER-PM contact sites in Drosophila adipocytes and regulates a sub-population of peripheral LDs (Ugrankar, Dev Cell, 2019). Thus, PXA domain-containing proteins appear to function as "metabolic tethers" that regulate LD biogenesis as well as LD attachment to other cellular compartments, thus controlling LD spatial organization and the interactions LDs have with other organelles.
Our work also dissects new and non-canonical roles of yeast nucleus-vacuole junctions (NVJs) as "metabolic platforms" that spatially organize metabolism. We find that NVJs act as sites of LD biogeneis (Hariri, EMBO reports, 2018; Hariri, JCB, 2019), as well as sites for the compartmentalization of mevalonate synthesis by HMG-CoA Reductases (Rogers, eLife, 2021). We also discovered that the expansion of NVJ contacts can be used to predict cell fates in response to nutrient stress. Yeast which expand their NVJs when faced with glucose starvation become quiescent, whereas yeast which fail to expand their NVJs become senescent (Wood, Cell Reports, 2020). These findings reveal NVJ inter-organelle contacts as important metabolic platforms for the organization of metabolism and cellular decision-making.
See more at our lab website: https://www.utsouthwestern.edu/labs/henne/
Background: Dr. Henne received his B.S. in Cellular and Molecular Biology from Texas Tech University in Lubbock, Texas, and then accepted a MRC Scholarship from the UK to pursue graduate studies at the MRC Laboratory of Molecular Biology at Cambridge University. As a student in the lab of Harvey McMahon, Ph.D., he studied how membrane sculpting BAR and F-BAR domain-containing proteins promote clathrin-mediated endocytosis. He characterized the F-BAR proteins FCHo1/2, and showed that they play crucial roles initiating clathrin vesicle biogenesis. Mike was awarded the Max Perutz Prize for his graduate work.
Following graduate school, Dr. Henne began a postdoctoral position in the laboratory of Scott Emr, Ph.D., at Cornell University as a Sam and Nancy Fleming Research Fellow. There, he continued to study endolysosomal trafficking, and how endosomes can be reshaped by the ESCRT (Endosomal Sorting Complexes Required for Transport) pathway. His work has focused on reconstituting and imaging ESCRT protein assemblies, and dissecting how they shape multi-vesicular endosomes. More recent projects involve global screens in yeast to identify novel proteins involved in endolysosomal trafficking.
Dr. Henne uses cell biology, biochemistry, structural biology, and genetics to understand the molecular mechanisms of LD dynamics, and the spatial organization of cellular lipid metabolism.
- inter-organelle communication
- lipid metabolism
- membrane sculpting
- Organelle homeostasis principles: How organelle quality control and inter-organelle crosstalk promote cell survival.
- Henne WM, Dev Cell 2021 Apr 56 7 878-880
- Glucose restriction drives spatial reorganization of mevalonate metabolism.
- Rogers SM, Hariri H, Wood NEM, Speer NO, Henne WM, Elife 2021 Apr 10
- Snx14 proximity labeling reveals a role in saturated fatty acid metabolism and ER homeostasis defective in SCAR20 disease.
- Datta S, Bowerman J, Hariri H, Ugrankar R, Eckert KM, Corley C, Vale G, McDonald JG, Henne WM, Proc Natl Acad Sci U S A 2020 Dec
- Nutrient Signaling, Stress Response, and Inter-organelle Communication Are Non-canonical Determinants of Cell Fate.
- Wood NE, Kositangool P, Hariri H, Marchand AJ, Henne WM, Cell Rep 2020 Dec 33 9 108446
- Drosophila Snazarus Regulates a Lipid Droplet Population at Plasma Membrane-Droplet Contacts in Adipocytes.
- Ugrankar R, Bowerman J, Hariri H, Chandra M, Chen K, Bossanyi MF, Datta S, Rogers S, Eckert KM, Vale G, Victoria A, Fresquez J, McDonald JG, Jean S, Collins BM, Henne WM, Dev. Cell 2019 Aug
- Mdm1 maintains endoplasmic reticulum homeostasis by spatially regulating lipid droplet biogenesis.
- Hariri H, Speer N, Bowerman J, Rogers S, Fu G, Reetz E, Datta S, Feathers JR, Ugrankar R, Nicastro D, Henne WM J. Cell Biol. 2019 Feb
- Cerebellar ataxia disease-associated Snx14 promotes lipid droplet growth at ER-droplet contacts.
- Datta S, Liu Y, Hariri H, Bowerman J, Henne WM J. Cell Biol. 2019 Feb
- Lipid droplet biogenesis is spatially coordinated at ER-vacuole contacts under nutritional stress.
- Hariri H, Rogers S, Ugrankar R, Liu YL, Feathers JR, Henne WM EMBO Rep. 2017 Nov
- Mdm1/Snx13 is a novel ER-endolysosomal interorganelle tethering protein.
- Henne WM, Zhu L, Balogi Z, Stefan C, Pleiss JA, Emr SD J. Cell Biol. 2015 Aug 210 4 541-51
- How NPC1 Loss Twists the TORCque of Lysosomes.
- Henne WM, Dev Cell 2021 Feb 56 3 251-252
Honors & Awards
- NIGMS R35/MIRA Award
- Searle Scholar
- Sam & Nancy Fleming Research Fellowship
- The Max Perutz Prize
awarded for Graduate work at MRC, Cambridge, UK (2009)