the Hekimi LAB

the Hekimi LAB

the Hekimi Lab: Publications

1. Hekimi, S. and O'Shea, M. (1987)

Identification of precursors of the insect neuropeptide adipokinetic hormone. J. Neurosci. 7(9):2773-2784

2. Hekimi, S. and O'Shea, M. (1989)

Biosynthesis of adipokinetic hormones (AKHs): further characterisation of precursors and identification of novel products of processing. J. Neurosci. 9(3):996-1004.

3. Hekimi, S. and O'Shea, M. (1989)

Antisera against AKHs and AKH precursors to study an insect neuroendocrine system. Insect Biochem. 19:79-83.

4. Hekimi, S., Burkhart, W., Moyer, M., Fowler, E. and O'Shea, M. (1989)

Dimer structure of neuropeptide precursor established: consequences for processing. Neuron, 2:1363-1368.

5. Hekimi, S. (1990)

A neuron-specific antigen in C.elegans allows visualization of the entire nervous system. Neuron, 4:855-865.

6. Hekimi, S., Fischer-Lougheed, J. and O'Shea, M. (1991)

Regulation of neuropeptide stoichiometry in neurosecretory cells. J. Neurosci. (10)11:3246-3257.

7. Hosono, R., Hekimi, S., Kamiya, Y., Sassa, T., Murakami, S., Nishiwaki, S., Miwa, J., Taketo, A. and Kodaira, K.-I. (1991)

The gene unc-18 encodes a novel protein affecting the kinetics of acetylcholine metabolism in the nematode C.elegans. J. Neurochem. 58(4):1517-1525.

8. Hekimi, S. and Kershaw D. (1993)

Axonal guidance defects in a Caenorhabditis elegans mutant reveal cell-extrinsic determinants of neuronal morphology. J. Neurosci. 13(10):4254-4272.

9. Wong A., Boutis P., and Hekimi S. (1995)

Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics, 139:1247-1259.

10. Barnes T., Kohara Y., Coulson A, and Hekimi S. (1995)

Meiotic recombination, non-coding DNA and genomic organization in Caenorhabditis elegans. Genetics, 141: 159-179

11. Hekimi S., Boutis P., and Lakowski B. (1995)

Viable, maternal-effect mutations which affect the development of the nematode Caenorhabditis elegans. Genetics, 141: 1351-1364.

12. Barnes TM, Yin Y, Horvitz HR, Ruvkun G, Hekimi S. (1996)

The C.elegans behavioural gene unc-24 encodes a novel bipartite protein similar to both
erythrocyte band 7.2 (stomatin) and non-specific lipid transfer protein (nsLTP). J Neurochemistry, 67(1): 46-57.

13. Lakowski B, Hekimi S. (1996) 

Determination of Life-Span in Caenorhabditis elegans by Four Clock Genes. Science, 272:1010-1013.

14. Ewbank JJ, Barnes TM, Lakowski B, Lussier M, Bussey H, Hekimi S (1997)

Structural and Functional Conservation of the C. elegans Clock Gene clk-1. Science, 279: 980-983.

15. Ogura K, Shirakawa M, Barnes T, Hekimi S, Ohshima Y (1997)

The UNC-14 protein required for axonal elongation and guidance in Caenorhabditis elegans interacts with the serine/threonine kinase UNC-51. Genes and Development, 11(14): 1801-1810.

16. Barnes T, Hekimi S (1997)

The C. elegans avermectin resistance and anesthetic response gene unc-9 encodes a member of a protein family implicated in
electrical coupling of excitable cells. J Neurochemistry, 69(6): 2251-2260.

17. Takagi S, Bénard C, Pak J, Livingstone D, Hekimi S (1997)

Cellular and axonal migrations are misguided along both body axes in the maternal-effect mau-2 mutants of Caenorhabditis elegans. Development, 124(24): 5115-5126.

18. Lakowski B, Hekimi S (1998)

The genetics of caloric restriction in C. elegans. Proceeding of the National Academy of Science of the USA, 22: 13091-13096

19. Labbé J-C, Hekimi S, Rokeach LA, (1998)

The levels of RoRNP-associated Y RNA are dependent upon the presence of ROP-1, the Caenorhabditis elegans Ro60 protein. Genetics, 151: 143-150.

20. Felkai S, Ewbank J, Lemieux J, Labbé J-C, Brown G, Hekimi S (1999) 

Control of respiration behavior and aging by the physiological clock gene clk-1. EMBO J, 18 (7): 1783-1792.

21. Whitfield CW, Benard C, Barnes T, Hekimi S, Kim SK (1999)

Basolateral localization of the C. elegans EGF receptor in epithelial cells by the PDZ protein LIN-10. Molecular Biology of the Cell, 10 (6):2087-100.

22. Labbé J-C, Burgess J, Rokeach L, Hekimi S (2000)

ROP-1, an RNA quality control pathway component, affects Caenorhabditis elegans dauer formation. Proceeding of the National Academy of Science of the USA, 97: 13233-38

23. Miyadera H, Amino H, Hiraishi A , Taka H, Murayama K, Miyoshi H, Sakamoto H, Ishii A, Hekimi S, Kita K (2001)

Altered quinone biosynthesis in the long-lived clk-1 mutants of Caenorhabditis elegans Journal of Biological Chemistry, 276:7713-7716.

24. Jiang N, Levavasseur F, McCright B, Shoubridge EA, Hekimi S (2001) 

Mouse CLK-1 is imported into mitochondria by an unusual process that requires a leader sequence but no membrane potential. Journal of Biological Chemistry, 276:29218-29225.

25. Lemieux J, Lakowski, Webb A, Barnes T, Meng Y, Hekimi S (2001)

Regulation of physiological rates in Caenorhabditis elegans by a tRNA modifying enzyme in the mitochondria. Genetics, 159: 147-157.

26. Bénard C, McCright B, Zhang Y, Felkai S, Lakowski B, Hekimi S (2001)

The C. elegans maternal-effect gene clk-2 affects developmental timing, is essential for embryonic development, encodes a protein homologous to yeast Tel2p, and is required for telomere length regulation. Development, 128 (20): 4045-4055.

27. Branicky R, Shibata Y, Feng J, Hekimi S (2001)

Suppressor analysis of clk-1 reveals that adaptation of behavior to changes in temperature is an active process in Caenorhabditis elegans.
Genetics, 159 (3): 997-1006.

28. Feng J, Bussière F, Hekimi S (2001)

Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Developmental Cell, 1(5): 633-44.

29. Levavasseur F, Miyadera H, Sirois J, Tremblay M, Kita K, Shoubridge E, Hekimi S (2001)

Ubiquinone is necessary for mouse embryonic development but is not essential for mitochondrial respiration. Journal of Biological Chemistry 276 (49):46160-4

30. Hihi A, Gao Y, Hekimi S (2002)

Ubiquinone is necessary for C. elegans development at mitochondrial and non-mitochondrial sites.Journal of Biological Chemistry 277(3):2202-6.

31. Jiang N, Bénard C, Kébir H, Shoubridge E, Hekimi S (2003)

hCLK2 links cell cycle progression, apoptosis and telomere length regulation. Journal of Biological Chemistry, 278(24):21678-84.

32. Hihi A, Kébir H, Hekimi S (2003)

Sensitivity of Caenorhabditis elegans clk-1 mutants to ubiquinone side-chain length reveals multiple ubiquinone-dependent processes. Journal of Biological Chemistry, 277(3):2202-6.

33. Shibata Y, Branicky R, Landaverde I, Hekimi S (2003)

Redox regulation of germline and vulval development in Caenorhabditis elegans. Science, 302(5651): 1779-82.

34. Burgess J, Hihi, A, Bénard C, Branicky R, Hekimi S (2003)

Molecular mechanism of maternal rescue in the clk-1 mutants of Caenorhabditis elegans. Journal of Biological Chemistry, 278(49): 49555-62.

35. De Jong L, Meng Y, Dent J, Hekimi S (2004)

Thiamine pyrophosphate biosynthesis and transport in the nematode Caenorhabditis elegans. Genetics,168(2):845-54.

36. Bénard C, Kébir H, Takagi S, and Hekimi S (2004)

mau-2 acts cell-autonomously to guide axonal migrations in Caenorhabditis elegans. Development,31:5947-58.

37. Liu, X, Jiang N, Hughes B, Bigras E, Shoubridge E, Hekimi S (2005)

Evolutionary conservation of the clk-1-dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice. Genes & Development, 19:2424-34.

38. Branicky R, Hekimi S (2005)

Specification of Muscle Neurotransmitter Sensitivity by a Paired-like Homeodomain Protein in C. elegans. Development, 132:4999-5009.

39. Branicky R, Nguyen P, Hekimi S (2006)

Uncoupling the pleiotropic phenotypes of clk-1 with tRNA missense suppressors in Caenorhabditis elegans. Molecular and Cellular Biology, 26:3976-85.

40. Seitan VC, Banks P, Laval S, Majid NA, Dorsett D, Rana A, Smith J, Bateman A, Krpic S, Hostert A, Rollins R, Erdjument-Bromage H,Tempst P, Benard CY, Hekimi S, Newbury S, Strachan T (2006)

Metazoan Scc4 homologues link sister chromatid cohesion to cell and axon migration guidance. PLoS Biology, 4(8):e242.

41. Yang W, Li J, Hekimi S (2007)

A measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the lifespan of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics, 177(4):2063-74.

42. Hihi AK, Beauchamp M-C, Branicky R, Desjardins A, Casanova I, Guimond M-P, Carroll M, Ethier M, Kianicka I, McBride K, and Hekimi S (2008)

Evolutionary conservation of drug action on lipoprotein metabolism-related targets. Journal of Lipid Research, 49(1):74-83.

43. Lapointe J, Hekimi S (2008)

Early mitochondrial dysfunction in long-lived Mclk1+/- mice. Journal of Biological Chemistry, 283(38):26217-27.

44. Wang Y, Branicky R, Stepanyan Z, Carroll M, Guimond M-P, Hihi A, Hayes S, McBride K, Hekimi S (2009)

The anti-neurodegeneration drug clioquinol inhibits the aging-associated protein CLK-1. Journal of Biological Chemistry, 284(1):314-23.

45. Lapointe J, Stepanyan Z, Bigras E, Hekimi S (2009)

Reversal of the mitochondrial phenotype and slow development of oxidative biomarkers of aging in long-lived Mclk1+/- mice. Journal of Biological Chemistry, 284(30):20364-74.

46. Van Raamsdonk J, Hekimi S (2009)

Deletion of sod-2 extends lifespan in C. elegans through the mitochondrial pathway. PLoS Genetics, 5(2): e1000361.

47. Hughes B, Hekimi S (2009)

Mclk1+/- Mice are not Resistant to the Development of Atherosclerosis. Lipids in Health and Disease, 8(1):16.

48. Wang D, Malo D, Hekimi S (2010)

Elevated mitochondrial ROS generation affects the immune response via HIF-1α in long-lived Mclk1+/- mouse mutants. Journal of Immunology, Jan 15;184(2):582-90. Epub 2009 Dec 9.

49. Van Raamsdonk J, Meng Y, Camp, Yang W, Jia X, Bénard C, Hekimi S (2010)

Decreased energy metabolism extends lifespan in Caenorhabditis elegans without reducing oxidative damage. Genetics, Jun;185(2):559-71. Epub 2010 Apr 9.

50. Yang W, Hekimi S (2010)

Two modes of mitochondrial dysfunction lead independently to lifespan extension in C. elegans. Aging Cell. Jun;9(3):433-47. Epub 2010 Mar 19.

51. Zheng H, Lapointe J, Hekimi S (2010) 

Life-long protection from global cerebral ischemia and reperfusion in long-lived Mclk1+/- mutants. Experimental Neurology. Jun;223(2):557-65.

52. Budinger GRS, Mutlu G, Urich D, Soberanes S, Buccellato L, Hawkins K, Chiarella S, Radigan K, Eisenbart J, Agrawal H, Berkelhamer S, Hekimi S, Zhang J, Perlman H, Schumacker P, Jain M, Chandel N (2011)

Epithelial Cell Death is an Important Contributor to Oxidant-Mediated Acute Lung Injury. American Journal of Respiratory and Critical Care Medicine. 183(8):1043-54.

53. Yang W, Hekimi S (2010)

A mitochondrial superoxide signal triggers longevity. PLoS Biology, 8(12): e1000556.

54. Hughes B, Hekimi S (2011)

A mild impairment of mitochondrial electron transport has sex-specific effects on lifespan and aging in mice. PLoS One, 6(10):e26116. 

55. Van Raamsdonk J, Hekimi S (2011)

FUdR causes a twofold increase in the lifespan of the mitochondrial mutant gas-1. Mechanisms of Aging and Development, 132(10):519-21.

56. Liu J-L, Desjardins D, Branicky R, Agellon LB, Hekimi S (2012)

Mitochondrial Oxidative Stress in C. elegans Alters a Pathway with Strong Similarities to that of Bile Acid Biosynthesis and Secretion in Vertebrates. PLoS Genetics, 8(3):e1002553.

57. Van Raamsdonk, Hekimi S (2012)

Superoxide dismutase is dispensable for normal animal lifespan. PNAS, 109(15):5785-90.

58. Robert F, Mills j, Agenor A, *Wang D, Di Marco S, Cencic R, Tremblay M, Gallouzi I, Hekimi S, Wing S, and Pelletier J. (2012)

Targeting Protein Synthesis in a Myc/mTOR-driven model of Anorexia-Cachexia Syndrome Delays Onset and Prolongs Survival. Cancer Research. Feb 1;72(3):747-56. Epub 2011 Dec 12.

59. Lapointe J, Wang Y, Bigras E, Hekimi S (2012)

The sub-mitochondrial distribution of ubiquinone affects respiration in long-lived Mclk1+/- mice. Journal of Cell Biology, Oct 15,199 (2).

60. Wang D, Wang Y, Argyriou C, Carrière A., Malo D. Hekimi S (2012)

An enhanced immune response of Mclk1+/- mutant mice is associated with partial protection from fibrosis, cancer and the development of biomarkers of aging. PLoS One, 7(11):e49606.

61. Wang Y, Hekimi S (2013)

Mitochondrial respiration without ubiquinone biosynthesis. Human Molecular Genetics, 2013 Dec 1;22(23):4768-83.

62. Yee C, Yang W, Hekimi S (2014)

The pro-longevity response to mitochondrial ROS in C. elegans is mediated by the intrinsic apoptosis pathway. CELL, May 8;157(4):897-909. doi: 10.1016/j.cell.2014.02.055.

63. Baruah A, Chang H, Hall M, Yuan J, Gordon S, Johnson E, Shtessel L, Yee C, Hekimi S, Derry WB, and Lee S (2014)

CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genetics, doi/pgen.1004097.

64. Wang Y, Oxer D, Hekimi S (2015)

Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nature Communications, Mar 6;6:6393. doi: 10.1038/ncomms7393.

65. Lapointe J, Hughes B, Bigras E, Hekimi S (2014)

Compensatory elevation of voluntary activity in mouse mutants with impaired mitochondrial energy metabolism. Physiological Reports, 2(11) e12214.

66. Claire E. Schaar, Dylan Dues, Katie Spielbauer, Emily Machiela, Jason Cooper, Megan Senchuk, Siegfried Hekimi, Jeremy M. Van Raamsdonk (2015)

Mitochondrial and Cytoplasmic ROS Have Opposing Effects on Lifespan.PLoS Genetics, Feb 11;11(2):e1004972. doi: 10.1371/journal.pgen.1004972.

67. Song P, Zhang W, Sobolevski A, Bernard K, Hekimi S, Liu X. (2015)

A microfluidic device for efficient chemical testing using Caenorhabditis elegans. Biomed Microdevices. Apr;17(2):9939. doi: 10.1007/s10544-015-9939-8.

68. Assaf Ben-Meir A, Burstein E, Borrego-Alvarez A, Chong J, Wong E, Yavorska T, Naranian T, Chi M, Wang Y, Bentov Y, Alexis J, Meriano J, Sung H-K, Gasser DL, Moley K, Hekimi S, Casper R, Jurisicova A (2015)

Coenzyme Q10 restores oocyte mitochondrial function and fertility during reproductive aging. Aging Cell, Doi: 10.1111/acel.1252.

69. Desjardins D, Cacho-Valadez B, Liu J-L, Wang Y, Yee C, Bernard K, Khaki A, Breton L and Hekimi S (2016) 

Antioxidants reveal an inverted U-shaped dose-
response relationship between ROS levels and the rate of aging in C. elegans. Aging Cell, Doi: 10.1111/acel.1252.
70. Hughes B, Hekimi S (2015)

Lifespan-extending genetic interventions slow the rate of aging in nematode but not in mice. PLoS Genetics, Under Revision.

71. Wang Y, Smith V, Parboosingh J, Khan S, Innes M, Hekimi S (2017)

Characterization of COQ7 mutations from two very different patients identifies treatment options and exclusions. J Cellular and Molecular Medicine, doi: 10.1111/jcmm.13154.

72. Liu JL, Yee C, Wang Y, Hekimi S (2017)

A single biochemical activity underlies the pleiotropy of the aging-related protein CLK-1. Scientific Reports, 7(1):859.

73. Blanchette CR, Thackeray A, Perrat PN, Hekimi S, Bénard CY (2017)

Functional requirements for heparan sulfate biosynthesis in morphogenesis and nervous system development in C. elegans. PLoS Genetics. doi: 10.1371/journal .pgen.1006525.

74. Hughes B, Hekimi S (2017)

Many possible maximum lifespan trajectories. Nature, In Press.