Team

Former Lab Members​

​Dr. MD Golam Mostofa (Postdoctoral Scholar)
Dr. Devesh Pant (Postdoctoral Scholar)
Dr. Muhammad Rahman (Postdoctoral Scholar)
Mohammad Kabir (Graduate Student)
Roberta Torinesi (Graduate Student)
​Sterling Neill (Graduate Student)
Andeep Kour (Graduate Student)

​Masangu Musau (Undergraduate Student)
​Enrique Sanchez (Undergraduate Student)
Diego Sunga (Undergraduate Student)
Victoria Carlino (Undergraduate Student)
Akshara Erasani (Undergraduate Student)
Makayla Nudo (Undergraduate Student)
Emem Akpan ​(Undergraduate Student)
Chetna Batra (Undergraduate Student)
​Praneetha Battu (Undergraduate Student)

Research

Our laboratory is studying lipophagy, the selective autophagy of lipid droplets (LDs). Although once perceived as inert structures, LDs have proven to be the dynamic organelles that hold many cellular functions. The LDs’ basic structure of a hydrophobic core consisting of neutral lipids and enclosed in a phospholipid monolayer allows for quick lipid accessibility for intracellular energy and membrane production. Whereas formed at the peripheral and perinuclear endoplasmic reticulum (ER), LDs are degraded either in the cytosol (by lipolysis) or in the vacuoles/lysosomes (by autophagy). Autophagy is a regulated breakdown of dysfunctional, damaged, or surplus cellular components. The selective autophagy of LDs is called lipophagy. We study LDs and their degradation by lipophagy in yeast, which proceeds via the micrometer-scale raft-like lipid domains in the vacuolar membrane. These vacuolar microdomains form during nutrient deprivation and facilitate internalization of LDs via the vacuolar membrane invagination and scission. The resultant intra-vacuolar autophagic bodies with LDs inside are broken down by vacuolar lipases and proteases. This type of lipophagy is called microlipophagy as it resembles microautophagy, the type of autophagy when substrates are sequestered right at the surface of a lytic compartment (Rahman et al., 2021).
Figure 1. Pathways that contribute to LD homeostasis in yeast. LD homeostasis is a sum of the anabolic (LD biogenesis from peripheral and perinuclear ER) and catabolic (LD degradation via cytosolic lipolysis and vacuolar lipophagy) processes. Under nutrient-rich conditions and absence of stressors, yeast cells possess a few small LDs associated with the ER. Starvation for carbon or nitrogen source induces LD biogenesis from the ER membranes, especially the nucleus–vacuole junction. The LDs grow and remain associated with the ER. During prolonged starvation, they can either be degraded in the cytosol by the LD-associated lipases or undergo microlipophagy and degradation in the vacuole by the vacuolar lipases and proteases. During lipolysis, LDs are often associated with peroxisomes (P) where fatty acids from LDs are catabolized via β-oxidation. Microlipophagy involves vacuolar docking of LDs at the newly formed raft-like microdomains followed by internalization of LDs via invagination and scission of the vacuolar membrane, and formation of the intravacuolar microlipophagic bodies that are then disintegrated by vacuolar hydrolases (Rahman et al., 2021).

Publications

  1. Nazarko TY. Autophagy of glycogen is non-selective in Komagataella phaffii. Autophagy Rep. 2024;3(1):2382659.
  2. Yakout DW, Shroff A, Wei W, Thaker V, Allen ZD, Sajish M, Nazarko TY, Mabb AM. Tau regulates Arc stability in neuronal dendrites via a proteasome-sensitive but ubiquitin-independent pathway. J Biol Chem. 2024 Mar 27:107237.
  3. Wijewantha NV, Kumar R, Nazarko TY. Glycogen Granules Are Degraded by Non-Selective Autophagy in Nitrogen-Starved Komagataella phaffii. Cells. 2024 Mar 7;13(6):467.
  4. Mensah TNA, Shroff A, Nazarko TY. Ubiquitin-binding autophagic receptors in yeast: Cue5 and beyond. Autophagy. 2023 Apr 16:1-5.
  5. Shroff A, Nazarko TY. SQSTM1, lipid droplets and current state of their lipophagy affairs. Autophagy. 2023 Feb;19(2):720-723. Epub 2022 Jul 7.
  6. Kumar R, Shroff A, Nazarko TY. Komagataella phaffii Cue5 Piggybacks on Lipid Droplets for Its Vacuolar Degradation during Stationary Phase Lipophagy. Cells. 2022 Jan 10;11(2):215.
  7. Anderson R, Agarwal A, Ghosh A, Guan BJ, Casteel J, Dvorina N, Baldwin WM 3rd, Mazumder B, Nazarko TY, Merrick WC, Buchner DA, Hatzoglou M, Kondratov RV, Komar AA. eIF2A-knockout mice reveal decreased life span and metabolic syndrome. FASEB J. 2021 Nov;35(11):e21990.
  8. Shroff A, Nazarko TY. The Molecular Interplay between Human Coronaviruses and Autophagy. Cells. 2021 Aug 7;10(8):2022.
  9. Rahman MA, Kumar R, Sanchez E, Nazarko TY. Lipid Droplets and Their Autophagic Turnover via the Raft-Like Vacuolar Microdomains. Int J Mol Sci. 2021 Jul 29;22(15):8144.
  10. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021 Jan;17(1):1-382.
  11. Nazarko TY. Special Issue on "Ubiquitin and Autophagy". Cells. 2021 Jan 10;10(1):116.
  12. Kumar R, Rahman MA, Nazarko TY. Nitrogen Starvation and Stationary Phase Lipophagy Have Distinct Molecular Mechanisms. Int J Mol Sci. 2020 Nov 29;21(23):9094.
  13. Pant DC, Nazarko TY. Selective autophagy: the rise of the zebrafish model. Autophagy. 2021 Nov;17(11):3297-3305. Epub 2020 Dec 15.
  14. Zientara-Rytter K, Ozeki K, Nazarko TY, Subramani S. Pex3 and Atg37 compete to regulate the interaction between the pexophagy receptor, Atg30, and the Hrr25 kinase. Autophagy. 2018;14(3):368-384.
  15. Nazarko TY. Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders. Autophagy. 2017 May 4;13(5):991-994.
  16. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1-222.
  17. Burnett SF, Farré JC, Nazarko TY, Subramani S. Peroxisomal Pex3 activates selective autophagy of peroxisomes via interaction with the pexophagy receptor Atg30. J Biol Chem. 2015 Mar 27;290(13):8623-31.
  18. Nazarko TY. Atg37 regulates the assembly of the pexophagic receptor protein complex. Autophagy. 2014 Jul;10(7):1348-9.
  19. Nazarko TY, Ozeki K, Till A, Ramakrishnan G, Lotfi P, Yan M, Subramani S. Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy. J Cell Biol. 2014 Feb 17;204(4):541-57.
  20. Nazarko TY, Farré JC. Molecular Machines Involved in Pexophagy. In: Brocard C, Hartig A, editors. Molecular Machines Involved in Peroxisome Biogenesis and Maintenance. Vienna: Springer; 2014. Chapter 22; p.481-506. 543p.
  21. Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr;8(4):445-544.
  22. Mijaljica D, Nazarko TY, Brumell JH, Huang WP, Komatsu M, Prescott M, Simonsen A, Yamamoto A, Zhang H, Klionsky DJ, Devenish RJ. Receptor protein complexes are in control of autophagy. Autophagy. 2012 Nov;8(11):1701-5.
  23. Nazarko VY, Nazarko TY, Farré JC, Stasyk OV, Warnecke D, Ulaszewski S, Cregg JM, Sibirny AA, Subramani S. Atg35, a micropexophagy-specific protein that regulates micropexophagic apparatus formation in Pichia pastoris. Autophagy. 2011 Apr;7(4):375-85.
  24. Manjithaya R, Nazarko TY, Farré JC, Subramani S. Molecular mechanism and physiological role of pexophagy. FEBS Lett. 2010 Apr 2;584(7):1367-73.
  25. Nazarko TY, Farré JC, Subramani S. Peroxisome size provides insights into the function of autophagy-related proteins. Mol Biol Cell. 2009 Sep;20(17):3828-39.
  26. Stasyk OV, Nazarko TY, Sibirny AA. Methods of plate pexophagy monitoring and positive selection for ATG gene cloning in yeasts. Methods Enzymol. 2008;451:229-39.
  27. Nazarko TY, Farré JC, Polupanov AS, Sibirny AA, Subramani S. Autophagy-related pathways and specific role of sterol glucoside in yeasts. Autophagy. 2007 May-Jun;3(3):263-5.
  28. Nazarko TY, Polupanov AS, Manjithaya RR, Subramani S, Sibirny AA. The requirement of sterol glucoside for pexophagy in yeast is dependent on the species and nature of peroxisome inducers. Mol Biol Cell. 2007 Jan;18(1):106-18.
  29. Krasovska OS, Babiak LI, Nazarko TY, Stasyk OG, Danysh TV, Gayda GZ, Stasyk OV, Gonchar MV, Sybirny AA. Construction of yeast Hansenula polymorpha overproducing amine oxidase as bioselective element of sensors for biogenic amines. In: El’skaya AV, Pokhodenko VD, editors. Investigations on Sensor Systems and Technologies. Kyiv: Institute of Molecular Biology and Genetics of NAS of Ukraine; 2006. p.141-8. 373p.
  30. Nazarko TY, Huang J, Nicaud JM, Klionsky DJ, Sibirny AA. Trs85 is required for macroautophagy, pexophagy and cytoplasm to vacuole targeting in Yarrowia lipolytica and Saccharomyces cerevisiae. Autophagy. 2005 Apr;1(1):37-45.
  31. Nazarko TIu, Sybirnyĭ AA. [Molecular mechanisms of autophagic peroxisome degradation in yeasts]. Ukr Biokhim Zh (1999). 2005 Mar-Apr;77(2):16-25. Ukrainian.
  32. Nazarko TY, Nicaud JM, Sibirny AA. Observation of the Yarrowia lipolytica peroxisome-vacuole dynamics by fluorescence microscopy with a single filter set. Cell Biol Int. 2005 Jan;29(1):65-70.
  33. Nazarko T, Mala M, Nicaud JM, Sibirny A. Mutants of the yeast Yarrowia lipolytica deficient in the inactivation of peroxisomal enzymes. Visnyk of L’viv Univ. Biology series. 2004; 35:128-36.
  34. Stasyk OV, Nazarko VY, Pochapinsky OD, Nazarko TY, Veenhuis M, Sibirny AA. Identification of intragenic mutations in the Hansenula polymorpha PEX6 gene that affect peroxisome biogenesis and methylotrophic growth. FEMS Yeast Res. 2003 Nov;4(2):141-7.
  35. Stasyk OV, Nazarko TY, Stasyk OG, Krasovska OS, Warnecke D, Nicaud JM, Cregg JM, Sibirny AA. Sterol glucosyltransferases have different functional roles in Pichia pastoris and Yarrowia lipolytica. Cell Biol Int. 2003;27(11):947-52.
  36. Ubiyvovk VM, Nazarko TY, Stasyk OG, Sohn MJ, Kang HA, Sibirny AA. GSH2, a gene encoding gamma-glutamylcysteine synthetase in the methylotrophic yeast Hansenula polymorpha. FEMS Yeast Res. 2002 Aug;2(3):327-32.
  37. Ubiĭvovk VM, Nazarko TIu, Stasyk EG, Sibirnyĭ AA. [Cloning of the GSH1 and GSH2 genes complementing the defective biosynthesis of glutathione in the methylotrophic yeast Hansenula polymorpha]. Mikrobiologiia. 2002 Nov-Dec;71(6):829-35. Russian.
  38. Nazarko VY, Pochapinsky OD, Nazarko TY, Stasyk OV, Sibirny AA. Isolation and characterization of cold sensitive pex6 mutant of the methylotrophic yeast Hansenula polymorpha. Biopolymers and Cell. 2002; 18(2):131-4.
  39. Nazarko TY, Mala MJ, Sibirny AA. Development of the plate assay screening procedure for isolation of the mutants deficient in inactivation of peroxisomal enzymes in the yeast Yarrowia lipolytica. Biopolymers and Cell. 2002; 18(2):135-8.

News

Contact

We are always looking for bright and motivated students and scholars.
Please reach out to us if you want to join the Nazarko Lab:

​Dr. Taras Nazarko
​Petit Science Center (PSC), Room 620
100 Piedmont Ave SE
Atlanta, GA 30303
Phone: 404-413-5349
E-mail: [email protected]
​
Copyright © Nazarko Lab 2021. All rights reserved.