SYSTEMS APPROACHES TO UNDERSTANDING MITOCHONDRIAL FUNCTION AND DYSFUNCTION IN DISEASE
Grant number: 1140851 | Funding period: 2018 - 2021
Mitochondria produce the energy for our bodies. Defects in this process cause mitochondrial disease, which affects at least 1/4300 people. Diagnosis is often inconclusive and few if any effective treatments exist. State of the art CRISPR gene-editing tools will be used to make disease models mimicking the different types of mitochondrial disease. These will be used to understand how mitochondria function, identify new disease genes and develop new drugs.
Related publications (10)
Fatal perinatal mitochondrial cardiac failure caused by recurrent de novo duplications in the ATAD3 locus.
Ann E Frazier, Alison G Compton, Yoshihito Kishita, Daniella H Hock, AnneMarie E Welch, Sumudu SC Amarasekera, Rocio Rius, Luke E Formosa, Atsuko Imai-Okazaki, David Francis, Min Wang, Nicole J Lake, Simone Tregoning, Jafar S Jabbari, Alexis Lucattini, Kazuhiro R Nitta, Akira Ohtake, Kei Murayama, David J Amor, George McGillivray
Background: In about half of all patients with a suspected monogenic disease, genomic investigations fail to identify the diagnosi..
Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10
Guy Helman, Alison G Compton, Daniella H Hock, Marzena Walkiewicz, Gemma R Brett, Lynn Pais, Tiong Y Tan, Ricardo De Paoli-Iseppi, Michael B Clark, John Christodoulou, Susan M White, David R Thorburn, David A Stroud, Zornitza Stark, Cas Simons
The diagnosis of Mendelian disorders following uninformative exome and genome sequencing remains a challenging and often unmet nee..
Mutations in the exocyst component EXOC2 cause severe defects in human brain development
Nicole J Van Bergen, Syed Mukhtar Ahmed, Felicity Collins, Mark Cowley, Annalisa Vetro, Russell C Dale, Daniella H Hock, Christian de Caestecker, Minal Menezes, Sean Massey, Gladys Ho, Tiziana Pisano, Seana Glover, Jovanka Gusman, David A Stroud, Marcel Dinger, Renzo Guerrini, Ian G Macara, John Christodoulou
The exocyst, an octameric protein complex, is an essential component of the membrane transport machinery required for tethering an..
HIGD2A is Required for Assembly of the COX3 Module of Human Mitochondrial Complex IV
Daniella H Hock, Boris Reljic, Ching-Seng Ang, Linden Muellner-Wong, Hayley S Mountford, Alison G Compton, Michael T Ryan, David R Thorburn, David A Stroud
Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the..
Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly Complex Factors in the Biogenesis of Complex I
Luke E Formosa, Linden Muellner-Wong, Boris Reljic, Alice J Sharpe, Thomas D Jackson, Traude H Beilharz, Diana Stojanovski, Michael Lazarou, David A Stroud, Michael T Ryan
Mitochondrial complex I harbors 7 mitochondrial and 38 nuclear-encoded subunits. Its biogenesis requires the assembly and integrat..
Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly
Shan Zhang, Boris Reljic, Chao Liang, Baptiste Kerouanton, Joel Celio Francisco, Jih Hou Peh, Camille Mary, Narendra Suhas Jagannathan, Volodimir Olexiouk, Claire Tang, Gio Fidelito, Srikanth Nama, Ruey-Kuang Cheng, Caroline Lei Wee, Loo Chien Wang, Paula Duek Roggli, Prabha Sampath, Lydie Lane, Enrico Petretto, Radoslaw M Sobota
The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end ..
The Mitochondrial Acyl-carrier Protein Interaction Network Highlights Important Roles for LYRM Family Members in Complex I and Mitoribosome Assembly
Marris G Dibley, Luke E Formosa, Baobei Lyu, Boris Reljic, Dylan McGann, Linden Muellner-Wong, Felix Kraus, Alice J Sharpe, David A Stroud, Michael T Ryan
NDUFAB1 is the mitochondrial acyl carrier protein (ACP) essential for cell viability. Through its pantetheine-4'-phosphate post-tr..
Function of hTim8a in complex IV assembly in neuronal cells provides insight into pathomechanism underlying Mohr-Tranebjaerg syndrome
Yilin Kang, Alexander J Anderson, Thomas Daniel Jackson, Catherine S Palmer, David P De Souza, Kenji M Fujihara, Tegan Stait, Ann E Frazier, Nicholas J Clemons, Deidreia Tull, David R Thorburn, Malcolm J McConville, Michael T Ryan, David A Stroud, Diana Stojanovski
Human Tim8a and Tim8b are members of an intermembrane space chaperone network, known as the small TIM family. Mutations in TIMM8A ..
Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6
Shadi Maghool, N Dinesha G Cooray, David A Stroud, David Aragao, Michael T Ryan, Megan J Maher
Assembly factors play key roles in the biogenesis of many multi-subunit protein complexes regulating their stability, activity, an..
OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect.
Kyle Thompson, Nicole Mai, Monika Oláhová, Filippo Scialó, Luke E Formosa, David A Stroud, Madeleine Garrett, Nichola Z Lax, Fiona M Robertson, Cristina Jou, Andres Nascimento, Carlos Ortez, Cecilia Jimenez-Mallebrera, Steven A Hardy, Langping He, Garry K Brown, Paula Marttinen, Robert McFarland, Alberto Sanz, Brendan J Battersby
OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase family, is required for the assembly of oxidative ..