Tigano Research

Tigano M, Vargas DC, Tremblay-Belzile S, Fu Y, Sfeir A. Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature. 2021 Mar;591(7850):477-481. doi: 10.1038/s41586-021-03269-w. Epub 2021 Feb 24. PMID: 33627873.

In this work we first describe how mitochondrial DNA double stranded breaks are conducive to innate immunity via mitochondrial herniation and release of mitochondrial RNA in the cytosol. The significance of this pathway is highlighted in the context of cellular irradiation, a standard of care cancer treatment.

Fu Y, Tigano M, Sfeir A. Safeguarding mitochondrial genomes in higher eukaryotes. Nat Struct Mol Biol. 2020 Aug;27(8):687-695. doi: 10.1038/s41594-020-0474-9. Epub 2020 Aug 6. PMID: 32764737.

In this review we discuss the state of the knowledge on mitochondrial DNA damage and repair and present perspectives on future research.

Phillips AF, Millet AR, Tigano M, Dubois SM, Crimmins H, Babin L, Charpentier M, Piganeau M, Brunet E, Sfeir A. Single-Molecule Analysis of mtDNA Replication Uncovers the Basis of the Common Deletion. Mol Cell. 2017 Feb 2;65(3):527-538.e6. doi: 10.1016/j.molcel.2016.12.014. Epub 2017 Jan 19. PMID: 28111015.

This manuscript provides, and for the first time, in-vivo data supporting the strand-displacement model of mtDNA replication. We develop and describe a new high-resolution single molecule technique to analyze mtDNA replication and deletion. We also describe the molecular details of mtDNA common deletion formation through the development and use of mitochondrial TALENs. 

Tigano M, Ruotolo R, Dallabona C, Fontanesi F, Barrientos A, Donnini C, Ottonello S. Elongator-dependent modification of cytoplasmic tRNALysUUU is required for mitochondrial function under stress conditions. Nucleic Acids Res. 2015 Sep 30;43(17):8368-80. doi: 10.1093/nar/gkv765. Epub 2015 Aug 3. PMID: 26240381; PMCID: PMC4787798.

In this manuscript we describe a genome-wide S. cerevisae deletion screening aimed to identify new genes essential for mitochondrial biogenesis under heat stress. We uncover how the cytosolic pathway of tRNA wobble base modification tailors cytoplasmic translation to maintain adequate mitochondrial function.

 Invernizzi F, Tigano M (Co-authorship), Dallabona C, Donnini C, Ferrero I, Cremonte M, Ghezzi D, Lamperti C, Zeviani M. “A Homozygous Mutation in LYRM7/MZM1L Associated with Early Onset Encephalopathy, Lactic Acidosis, and Severe Reduction of Mitochondrial Complex III Activity”. Hum Mutat. 2013 Sep 6.

This publication is an example of the power of tailored S. cerevisiae models in determining the pathogenicity of human mutations in mitochondrial genes. This approach was the gold-standard in pre-CRISPR era, and still extremely informative when working with essential genes.