Held, James et al. (2021) International Worm Meeting "Homolog of ELAC2 is responsive to mitochondrial stress and activates the mitochondrial unfolded protein response"

Patel, Maulik, Held, James

[International Worm Meeting, 2021]

Proper mitochondrial function is imperative for cell health and homeostasis. Defects in mitochondrial function have profound impacts on aging and have been associated with a growing list of diseases and disorders. To maintain mitochondrial function, cellular mechanisms have evolved that are responsive to mitochondrial stress. However, the molecular underpinnings of these mechanisms are poorly understood. Using a targeted screening approach, we have discovered that the tRNA processing enzyme HOE-1 (homolog of ELAC2) is responsive to mitochondrial stress. Upon mitochondrial stress, nuclear levels of HOE-1 are elevated. We find that HOE-1 is integral for the activation of an important stress mechanism called the mitochondrial unfolded protein response (UPRmt). Loss of HOE-1 attenuates UPRmt induction, while forcing its nuclear accumulation is sufficient to robustly induce UPRmt, even in the absence of mitochondrial stress. Blocking tRNA export from the nucleus is sufficient to suppress HOE-1 dependent UPRmt induction. These data suggest that HOE-1 generates tRNA species required in the cytosol to trigger UPRmt. Taken together we have identified a novel and unusual pathway of UPRmt activation. Our work provides a better understanding of how cells sense and respond to mitochondrial stress.

Butler JA et al. (1994) Worm Breeder's Gazette "Looking For Extracellular Matrix Proteinases in C. elegans"

Kramer JM, Butler JA

[Worm Breeder's Gazette, 1994]

LOOKING FOR EXTRACELLULAR MATRIX PROTEINASES IN C. ELEGANS. James A. Butler and James M. Kramer, Northwestern University Medical School. Department of CMS Biology, Chicago IL 60611

Wissmann AK et al. (1994) Worm Breeder's Gazette "Characterization of the let-502 Gene"

Mains PE, Wissmann AK, McGhee JD

[Worm Breeder's Gazette, 1994]

Characterization of the let-502 gene Andreas Wissmann, James D. McGhee and Paul E. Mains, Dept. of Medical Biochemistry, University of Calgary, Calgary, Alberta, Canada T2N 4N1

Cordero F et al. (2019) BMC Bioinformatics "BITS2018: the fifteenth annual meeting of the Italian Society of Bioinformatics."

Cordero F, Calogero RA, Caselle M

[BMC Bioinformatics, 2019]

This preface introduces the content of the BioMed Central Bioinformatics journal Supplement related to the 15th annual meeting of the Bioinformatics Italian Society, BITS2018. The Conference was held in Torino, Italy, from June 27th to 29th, 2018.

Pessoa J (2022) Trends Endocrinol Metab "Shifting metabolism to increase lifespan."

Pessoa J

[Trends Endocrinol Metab, 2022]

Lionaki et al. report that reducing mitochondrial protein import increases Caenorhabditis elegans lifespan, through a metabolic shift that enhances the conversion of glucose into serine. Here, I discuss the promise held by these findings in the framework of therapeutic approaches to metabolic and neurodegenerative diseases.

Teng X et al. (2010) Cell "The apoptosome at high resolution."

Hardwick JM, Teng X

[Cell, 2010]

The mechanism by which the apoptosome activates caspases during apoptosis has been controversial. Qi et al. (2010) now present a crystal structure of a funnel-shaped octameric apoptosome complex from the nematode Caenorhabditis elegans that challenges currently held assumptions about the human apoptosome structure.

Pereira, Claudia V. et al. (2021) International Worm Meeting "Unraveling the role of clk-1 in the modulation of mtDNA heteroplasmy"

Pereira, Claudia V., Patel, Maulik R., Held, James P.

[International Worm Meeting, 2021]

The mitochondrial genome is prone to mutations and deletions that persist throughout generations despite germline selection mechanisms. Therefore, copies of wild-type and mutant mtDNA molecules can co-exist within the same cell or organism, which is termed heteroplasmy. Mitochondrial disease can manifest when a certain threshold for the levels of mutation is surpassed. Since there are multiple copies of mtDNA per cell, the mtDNA copy number can vary in different cells and tissues, according to their energetic demands. Previously, we have found that the wild-type mtDNA copy number is maintained despite an elevation in the total mtDNA levels, in the well characterized heteroplasmic C. elegans strain, uaDf5. This suggests the existence of a homeostatic copy number regulation mechanism to maintain the wild-type mtDNA levels in C. elegans, whereas the mutant mtDNA escapes this control. The mechanisms that dictate the persistence and propagation of deleterious mutations and the regulation of mtDNA copy number, remain to be elucidated. Previous work showed that CLK-1, a protein that participates in the ubiquinone biosynthesis pathway can bind mtDNA in vitro. Recently, our group found that ubiquinone deficient clk-1(ok1247) mutant worms display an elevated total mtDNA copy number which is not normalized to control levels in the presence of the ubiquinone precursor, 2-4-dihydroxybenzoate (DHB), suggesting an additional role for this protein. In this study, we aim to first determine if clk-1 is capable of modulating mtDNA heteroplasmy frequency in uaDf5 heteroplasmic worms, by crossing clk-1(ok1247) mutant with uaDf5 worms and, evaluating the heteroplasmy frequency by quantitative ddPCR. These experiments were performed in the presence of 10mM DHB, to guarantee clk-1 mutants are supplemented with ubiquinone. Our results show that clk-1 (ok1247) mutant; uaDf5 worms have in average significantly lower mutant mtDNA frequency than wild-type; uaDf5 worms. Furthermore, we have also performed the same experiments with clk-1(e2519) catalytic mutant worms, as another way to demonstrate our results were unrelated with clk-1 canonical function. Our work shows CLK-1 to be involved in mtDNA heteroplasmy dynamics and possibly, mtDNA copy number regulation.

Howells RE et al. (1991) Parasitol Today "Caenorhabditis elegans: A model for parasitic nematodes."

Johnstone IL, Howells RE

[Parasitol Today, 1991]

The free-living nematode Caenorhabditis elegans offers many advantages as an experimental system and extensive similarities in overall structure and development exist between it and parasitic nematodes. The purpose of the meeting held at Broadway, 17-20 February 1991, with the financial support of the Wellcome Trust, was to stimulate interaction between schools of nematologists.

Laskey R et al. (1977) Nature "Genes in development."

Laskey R, Lawrence P, De Robertis E

[Nature, 1977]

Participants in two days of talks held at the Accademia Lincei in Rome-the oldest scientific foundatin in the modern world, tried to tackle the ancient problem of how eggs plus genes produce animals. It was symptomatic of the renewed interest in Drosophila that the whole of the first day was devoted to that fly...

Szabad J (2010) EMBO Rep "Putting together rather than taking apart."

Szabad J

[EMBO Rep, 2010]

The town of Ascona in Switzerland, nestled on the northern shore of Lago Maggiore, hosted the 112 participants in the first systems biology meeting focused on developmental biology. The EMBO workshop was held between 16 and 20 August and brought together a multidisciplinary group of scientists who use systems approaches to understand how the size and shape of multicellular organisms and organs are determined.