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1,254 results on '"Lippincott-Schwartz, Jennifer"'

1. Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome

Author

Venkatraman, Kailash, Lee, Christopher T, Garcia, Guadalupe C, Mahapatra, Arijit, Milshteyn, Daniel, Perkins, Guy, Kim, Keun‐Young, Pasolli, H Amalia, Phan, Sebastien, Lippincott‐Schwartz, Jennifer, Ellisman, Mark H, Rangamani, Padmini, and Budin, Itay

Subjects
Biochemistry and Cell Biology, Biological Sciences, Bioengineering, cardiolipin, cristae, lipids, mechanics, mitochondria, Information and Computing Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Cristae are high-curvature structures in the inner mitochondrial membrane (IMM) that are crucial for ATP production. While cristae-shaping proteins have been defined, analogous lipid-based mechanisms have yet to be elucidated. Here, we combine experimental lipidome dissection with multi-scale modeling to investigate how lipid interactions dictate IMM morphology and ATP generation. When modulating phospholipid (PL) saturation in engineered yeast strains, we observed a surprisingly abrupt breakpoint in IMM topology driven by a continuous loss of ATP synthase organization at cristae ridges. We found that cardiolipin (CL) specifically buffers the inner mitochondrial membrane against curvature loss, an effect that is independent of ATP synthase dimerization. To explain this interaction, we developed a continuum model for cristae tubule formation that integrates both lipid and protein-mediated curvatures. This model highlighted a snapthrough instability, which drives IMM collapse upon small changes in membrane properties. We also showed that cardiolipin is essential in low-oxygen conditions that promote PL saturation. These results demonstrate that the mechanical function of cardiolipin is dependent on the surrounding lipid and protein components of the IMM.

Published
2023

3. Author Correction: Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress

Author

Liu, Xihui, Viswanadhapalli, Suryavathi, Kumar, Shourya, Lee, Tae-Kyung, Moore, Andrew, Ma, Shihong, Chen, Liping, Hsieh, Michael, Li, Mengxing, Sareddy, Gangadhara R., Parra, Karla, Blatt, Eliot B., Reese, Tanner C., Zhao, Yuting, Chang, Annabel, Yan, Hui, Xu, Zhenming, Pratap, Uday P., Liu, Zexuan, Roggero, Carlos M., Tan, Zhenqiu, Weintraub, Susan T., Peng, Yan, Tekmal, Rajeshwar R., Arteaga, Carlos L., Lippincott-Schwartz, Jennifer, Vadlamudi, Ratna K., Ahn, Jung-Mo, and Raj, Ganesh V.

Published
2024
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4. YAP condensates are highly organized hubs

Author

Hao, Siyuan, Lee, Ye Jin, Benhamou Goldfajn, Nadav, Flores, Eduardo, Liang, Jindayi, Fuehrer, Hannah, Demmerle, Justin, Lippincott-Schwartz, Jennifer, Liu, Zhe, Sukenik, Shahar, and Cai, Danfeng

Published
2024
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9. Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress

Author

Liu, Xihui, Viswanadhapalli, Suryavathi, Kumar, Shourya, Lee, Tae-Kyung, Moore, Andrew, Ma, Shihong, Chen, Liping, Hsieh, Michael, Li, Mengxing, Sareddy, Gangadhara R., Parra, Karla, Blatt, Eliot B., Reese, Tanner C., Zhao, Yuting, Chang, Annabel, Yan, Hui, Xu, Zhenming, Pratap, Uday P., Liu, Zexuan, Roggero, Carlos M., Tan, Zhenqiu, Weintraub, Susan T., Peng, Yan, Tekmal, Rajeshwar R., Arteaga, Carlos L., Lippincott-Schwartz, Jennifer, Vadlamudi, Ratna K., Ahn, Jung-Mo, and Raj, Ganesh V.

Published
2022
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12. De novo design of tunable, pH-driven conformational changes

Author

Boyken, Scott E, Benhaim, Mark A, Busch, Florian, Jia, Mengxuan, Bick, Matthew J, Choi, Heejun, Klima, Jason C, Chen, Zibo, Walkey, Carl, Mileant, Alexander, Sahasrabuddhe, Aniruddha, Wei, Kathy Y, Hodge, Edgar A, Byron, Sarah, Quijano-Rubio, Alfredo, Sankaran, Banumathi, King, Neil P, Lippincott-Schwartz, Jennifer, Wysocki, Vicki H, Lee, Kelly K, and Baker, David

Subjects
Biochemistry and Cell Biology, Chemical Sciences, Biological Sciences, Generic health relevance, Hydrogen-Ion Concentration, Protein Conformation, Protein Engineering, Protein Multimerization, Protein Stability, General Science & Technology
Abstract

The ability of naturally occurring proteins to change conformation in response to environmental changes is critical to biological function. Although there have been advances in the de novo design of stable proteins with a single, deep free-energy minimum, the design of conformational switches remains challenging. We present a general strategy to design pH-responsive protein conformational changes by precisely preorganizing histidine residues in buried hydrogen-bond networks. We design homotrimers and heterodimers that are stable above pH 6.5 but undergo cooperative, large-scale conformational changes when the pH is lowered and electrostatic and steric repulsion builds up as the network histidine residues become protonated. The transition pH and cooperativity can be controlled through the number of histidine-containing networks and the strength of the surrounding hydrophobic interactions. Upon disassembly, the designed proteins disrupt lipid membranes both in vitro and after being endocytosed in mammalian cells. Our results demonstrate that environmentally triggered conformational changes can now be programmed by de novo protein design.

Published
2019

14. An open-access volume electron microscopy atlas of whole cells and tissues

Author

Xu, C. Shan, Pang, Song, Shtengel, Gleb, Müller, Andreas, Ritter, Alex T., Hoffman, Huxley K., Takemura, Shin-ya, Lu, Zhiyuan, Pasolli, H. Amalia, Iyer, Nirmala, Chung, Jeeyun, Bennett, Davis, Weigel, Aubrey V., Freeman, Melanie, van Engelenburg, Schuyler B., Walther, Tobias C., Farese, Jr., Robert V., Lippincott-Schwartz, Jennifer, Mellman, Ira, Solimena, Michele, and Hess, Harald F.

Published
2021
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17. Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome

Author

Venkatraman, Kailash, primary, Lee, Christopher T, additional, Garcia, Guadalupe C, additional, Mahapatra, Arijit, additional, Milshteyn, Daniel, additional, Perkins, Guy, additional, Kim, Keun‐Young, additional, Pasolli, H Amalia, additional, Phan, Sebastien, additional, Lippincott‐Schwartz, Jennifer, additional, Ellisman, Mark H, additional, Rangamani, Padmini, additional, and Budin, Itay, additional

Published
2023
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18. Nanometer-scale views of visual cortex reveal anatomical features of primary cilia poised to detect synaptic spillover

Author

Ott, Carolyn M., primary, Torres, Russel, additional, Kuan, Tung-Sheng, additional, Kuan, Aaron, additional, Buchanan, JoAnn, additional, Elabbady, Leila, additional, Seshamani, Sharmishtaa, additional, Bodor, Agnes L., additional, Collman, Forrest, additional, Bock, Davi D., additional, Lee, Wei Chung, additional, Maçarico da Costa, Nuno, additional, and Lippincott-Schwartz, Jennifer, additional

Published
2023
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21. AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation.

Author

Seo, Arnold Y, Lau, Pick-Wei, Feliciano, Daniel, Sengupta, Prabuddha, Gros, Mark A Le, Cinquin, Bertrand, Larabell, Carolyn A, and Lippincott-Schwartz, Jennifer

Subjects
Saccharomyces cerevisiae, Protein Kinases, Glucose, Saccharomyces cerevisiae Proteins, Energy Metabolism, Autophagy, Microbial Viability, Lipid Metabolism, Autophagy-Related Proteins, AMPK, ATG14, S. cerevisiae, cell biology, lipid-droplets, microautophagy, starvation-induced lifespan extension, vacuole-membrane domains, Aging, Nutrition, 1.1 Normal biological development and functioning, Biochemistry and Cell Biology
Abstract

Dietary restriction increases the longevity of many organisms, but the cell signaling and organellar mechanisms underlying this capability are unclear. We demonstrate that to permit long-term survival in response to sudden glucose depletion, yeast cells activate lipid-droplet (LD) consumption through micro-lipophagy (µ-lipophagy), in which fat is metabolized as an alternative energy source. AMP-activated protein kinase (AMPK) activation triggered this pathway, which required Atg14p. More gradual glucose starvation, amino acid deprivation or rapamycin did not trigger µ-lipophagy and failed to provide the needed substitute energy source for long-term survival. During acute glucose restriction, activated AMPK was stabilized from degradation and interacted with Atg14p. This prompted Atg14p redistribution from ER exit sites onto liquid-ordered vacuole membrane domains, initiating µ-lipophagy. Our findings that activated AMPK and Atg14p are required to orchestrate µ-lipophagy for energy production in starved cells is relevant for studies on aging and evolutionary survival strategies of different organisms.

Published
2017

24. Mitochondrial protein FKBP8 captures PDZD8 to form mitochondria-ER contacts

Author

Nakamura, Koki, primary, Aoyama-Ishiwatari, Saeko, additional, Nagao, Takahiro, additional, Paaran, Mohammadreza, additional, Obara, Christopher J, additional, Sakurai-Saito, Yui, additional, Johnston, Jake, additional, Du, Yudan, additional, Suga, Shogo, additional, Tsuboi, Masafumi, additional, Nakakido, Makoto, additional, Tsumoto, Kouhei, additional, Kishi, Yusuke, additional, Gotoh, Yukiko, additional, Kwak, Chulhwan, additional, Rhee, Hyun-Woo, additional, Seo, Jeong Kon, additional, Kosako, Hidetaka, additional, Potter, Clint, additional, Carragher, Bridget, additional, Lippincott-Schwartz, Jennifer, additional, Polleux, Franck, additional, and Hirabayashi, Yusuke, additional

Published
2023
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31. Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution

Author

Chen, Bi-Chang, Legant, Wesley R, Wang, Kai, Shao, Lin, Milkie, Daniel E, Davidson, Michael W, Janetopoulos, Chris, Wu, Xufeng S, Hammer, John A, Liu, Zhe, English, Brian P, Mimori-Kiyosue, Yuko, Romero, Daniel P, Ritter, Alex T, Lippincott-Schwartz, Jennifer, Fritz-Laylin, Lillian, Mullins, R Dyche, Mitchell, Diana M, Bembenek, Joshua N, Reymann, Anne-Cecile, Böhme, Ralph, Grill, Stephan W, Wang, Jennifer T, Seydoux, Geraldine, Tulu, U Serdar, Kiehart, Daniel P, and Betzig, Eric

Subjects
Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Caenorhabditis elegans, Cell Communication, Drosophila melanogaster, Embryo, Nonmammalian, Embryonic Stem Cells, Imaging, Three-Dimensional, Mice, Microscopy, Molecular Imaging, Spheroids, Cellular, General Science & Technology
Abstract

Although fluorescence microscopy provides a crucial window into the physiology of living specimens, many biological processes are too fragile, are too small, or occur too rapidly to see clearly with existing tools. We crafted ultrathin light sheets from two-dimensional optical lattices that allowed us to image three-dimensional (3D) dynamics for hundreds of volumes, often at subsecond intervals, at the diffraction limit and beyond. We applied this to systems spanning four orders of magnitude in space and time, including the diffusion of single transcription factor molecules in stem cell spheroids, the dynamic instability of mitotic microtubules, the immunological synapse, neutrophil motility in a 3D matrix, and embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. The results provide a visceral reminder of the beauty and the complexity of living systems.

Published
2014

33. LKB1/AMPK and PKA control ABCB11 trafficking and polarization in hepatocytes.

Author

Homolya, László, Fu, Dong, Sengupta, Prabuddha, Jarnik, Michal, Gillet, Jean-Pierre, Vitale-Cross, Lynn, Gutkind, J, Lippincott-Schwartz, Jennifer, and Arias, Irwin

Subjects
AMP-Activated Protein Kinases, ATP Binding Cassette Transporter, Subfamily B, Member 11, ATP-Binding Cassette Transporters, Animals, Bile Acids and Salts, Cell Membrane, Cell Polarity, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Endosomes, Gene Expression Regulation, Golgi Apparatus, Hepatocytes, Mice, Mice, Knockout, Myosin Type V, Primary Cell Culture, Protein Serine-Threonine Kinases, Protein Transport, Signal Transduction, Taurocholic Acid, rab GTP-Binding Proteins
Abstract

Polarization of hepatocytes is manifested by bile canalicular network formation and activation of LKB1 and AMPK, which control cellular energy metabolism. The bile acid, taurocholate, also regulates development of the canalicular network through activation of AMPK. In the present study, we used collagen sandwich hepatocyte cultures from control and liver-specific LKB1 knockout mice to examine the role of LKB1 in trafficking of ABCB11, the canalicular bile acid transporter. In polarized hepatocytes, ABCB11 traffics from Golgi to the apical plasma membrane and endogenously cycles through the rab 11a-myosin Vb recycling endosomal system. LKB1 knockout mice were jaundiced, lost weight and manifested impaired bile canalicular formation and intracellular trafficking of ABCB11, and died within three weeks. Using live cell imaging, fluorescence recovery after photobleaching (FRAP), particle tracking, and biochemistry, we found that LKB1 activity is required for microtubule-dependent trafficking of ABCB11 to the canalicular membrane. In control hepatocytes, ABCB11 trafficking was accelerated by taurocholate and cAMP; however, in LKB1 knockout hepatocytes, ABCB11 trafficking to the apical membrane was greatly reduced and restored only by cAMP, but not taurocholate. cAMP acted through a PKA-mediated pathway which did not activate AMPK. Our studies establish a regulatory role for LKB1 in ABCB11 trafficking to the canalicular membrane, hepatocyte polarization, and canalicular network formation.

Published
2014

39. Publisher Correction: An open-access volume electron microscopy atlas of whole cells and tissues

Author

Xu, C. Shan, Pang, Song, Shtengel, Gleb, Müller, Andreas, Ritter, Alex T., Hoffman, Huxley K., Takemura, Shin-ya, Lu, Zhiyuan, Pasolli, H. Amalia, Iyer, Nirmala, Chung, Jeeyun, Bennett, Davis, Weigel, Aubrey V., Freeman, Melanie, van Engelenburg, Schuyler B., Walther, Tobias C., Farese, Jr., Robert V., Lippincott-Schwartz, Jennifer, Mellman, Ira, Solimena, Michele, and Hess, Harald F.

Published
2021
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41. Primary cilia utilize glycoprotein-dependent adhesion mechanisms to stabilize long-lasting ilia-cilia contacts

Author

Ott, Carolyn, Elia, Natalie, Jeong, Suh, Insinna, Christine, Sengupta, Prabuddha, and Lippincott-Schwartz, Jennifer

Abstract

Abstract Background The central tenet of cilia function is sensing and transmitting information. The capacity to directly contact extracellular surfaces would empower primary cilia to probe the environment for information about the nature and location of nearby surfaces. It has been well established that flagella and other motile cilia perform diverse cellular functions through adhesion. We hypothesized that mammalian primary cilia also interact with the extracellular environment through direct physical contact. Methods We identified cilia in rod photoreceptors and cholangiocytes in fixed mouse tissues and examined the structures that these cilia contact in vivo. We then utilized an MDCK cell culture model to characterize the nature of the contacts we observed. Results In retina and liver tissue, we observed that cilia from nearby cells touch one another. Using MDCK cells, we found compelling evidence that these contacts are stable adhesions that form bridges between two cells, or networks between many cells. We examined the nature and duration of the cilia-cilia contacts and discovered primary cilia movements that facilitate cilia-cilia encounters. Stable adhesions form as the area of contact expands from a single point to a stretch of tightly bound, adjacent cilia membranes. The cilia-cilia contacts persisted for hours and were resistant to several harsh treatments such as proteases and DTT. Unlike many other cell adhesion mechanisms, calcium was not required for the formation or maintenance of cilia adhesion. However, swainsonine, which blocks maturation of N-linked glycoproteins, reduced contact formation. We propose that cellular control of adhesion maintenance is active because cilia adhesion did not prevent cell division; rather, contacts dissolved during mitosis as cilia were resorbed. Conclusions The demonstration that mammalian primary cilia formed prolonged, direct, physical contacts supports a novel paradigm: that mammalian primary cilia detect features of the extracellular space, not just as passive antennae, but also through direct physical contact. We present a model for the cycle of glycoprotein-dependent contact formation, maintenance, and termination, and discuss the implications for potential physiological functions of cilia-cilia contacts.

Published
2012

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