2019Loss of the mitochondrial -AAA protease YME1L leads to ocular dysfunction and spinal axonopathy, EMBO Mol Med 2019 Jan;11(1).
2017Lung ultrasound as a translational approach for non-invasive assessment of heart failure with reduced or preserved ejection fraction in mice, Cardiovasc. Res. 2017 Aug;113(10):1113-1123.
2016The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L, EMBO Rep. 2016 12;17(12):1844-1856.
2016Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation, Elife 2016 08;5.
2016Mitochondrial Dynamics and Metabolic Regulation, Trends Endocrinol. Metab. 2016 Feb;27(2):105-117.
2015Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice, Science 2015 Dec;350(6265):aad0116.
2015SLIRP Regulates the Rate of Mitochondrial Protein Synthesis and Protects LRPPRC from Degradation, PLoS Genet. 2015 Aug;11(8):e1005423.
2015Stomatin-like protein 2 is required for in vivo mitochondrial respiratory chain supercomplex formation and optimal cell function, Mol. Cell. Biol. 2015 May;35(10):1838-47.
2015The Mitochondrial Metallochaperone SCO1 Is Required to Sustain Expression of the High-Affinity Copper Transporter CTR1 and Preserve Copper Homeostasis, Cell Rep 2015 Feb;.
2014The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission, J. Cell Biol. 2014 Mar;204(6):919-29.
+View full list of publications
The research focus of the lab is to understand the complex interplay of mitochondrial dynamics and metabolism in health and disease. Mitochondria are essential organelles whose morphology varies tremendously across cell types and tissues. Balanced fusion and fission events shape mitochondria to meet metabolic demands and to ensure removal of damaged organelles. The dynamism of mitochondria is highlighted by the dramatic changes in morphology they undergo in response to metabolic inputs. Mitochondrial fragmentation occurs in response to nutrient excess and cellular dysfunction and has been observed in cardiovascular and neuromuscular disorders, cancer, and obesity. The morphology of mitochondria is inextricably linked to its many essential functions in the cell and we are interested in understanding the relationship between mitochondrial shape changes and metabolism in the context of acquired and inborn human diseases
Objectives. Mitochondria are essential organelles whose morphology varies tremendously across cell types. The physiological relevance of mitochondrial morphology and the mechanisms that regulate mitochondrial dynamics in vivo are poorly understood. We seek to:
• Identify the metabolic signals that balance mitochondrial fusion and fission
• Define the molecular mechanisms of stress-induced fission
• Design strategies aimed at re-balancing mitochondrial dynamics in vivo
• Translate our experimental findings to acquired and inborn human diseases
Strategy. Our research strategy builds upon frontier science in the areas of cell biology and biochemistry of mitochondria. We apply this knowledge to preclinical animal models and cellular models derived from patient biopsies to address fundamental translational knowledge gaps in rare genetic diseases of metabolism as well as common acquired age-associated diseases which include cardiovascular disease, cancer, and neurodegeneration.
Timothy Wai email@example.com Institut Pasteur 25-28 Rue du Docteur Roux 75015