Venue: Centre Broca
Anthonny S. Grillo
Department of Chemistry – Chair, Biochemistry Division
Univ. Cincinnati, USA
https://www.grillolabuc.com/
Title
A mitochondrial Complex I deficiency induces iron accumulation and tau aggregation.
Abstract
Mitochondrial bioenergetic deficiencies are one of the earliest features of most age-related diseases such as Alzheimer’s disease, Parkinson’s disease, and ALS. Despite its pervasive recognition as a hallmark of these neurodegenerative diseases, there remains an urgent need to understand the multivariate influences mitochondrial dysfunction has on the molecular determinants that elicit biologic decline. We and others hypothesize age-related reductions in the Electron Transport Chain
activity cause metabolic O2 imbalances or iron accumulation that is associated with neuroinflammation in dementia and movement disorders. We discovered mice missing mitochondrial Complex I show O2-dependent accumulation of tau, and that housing mice in low oxygen environments can prevent tau pathogenicity. Further, Complex I deficiencies induce the
accumulation and misregulation of iron to drive inflammation. Collectively, this work suggests mitochondrial Complex I deficiencies may induce the pathogenic accumulation of proteins or metals involved in tauopathies with Parkinsonism-like features such as Progressive Supranuclear Palsy.
Biography:
Dr. Grillo was born in Michigan, USA before obtaining a B.S. in Biochemistry and a B.S. in Chemistry from the University of Michigan. He began graduate studies in Marty Burke’s Lab at the University of Illinois at Urbana-Champaign as an NSF Predoctoral Fellow (NSF GRFP) and obtained his Ph.D. with a focus on Chemical Biology in 2017. His thesis centered on the discovery, development, and mechanistic understanding of small molecules that mimic protein function to restore physiology to protein-deficient organisms, thereby acting as prostheses on the molecular scale. As an NRSA Postdoctoral Fellow and Alzheimer’s Disease Research Center Trainee in Matt Kaeberlein’s Lab at the University of Washington, Dr. Grillo elucidated the role of protein kinase C in promoting neuroinflammation in mice missing Complex I of the Electron Transport Chain and probed the etiology of mitochondrial dysfunction in tauopathies and movement disorders. He joined the University of Cincinnati Department of Chemistry (Biochemistry Division) in 2022 as an Assistant Professor. Interdisciplinary research in the Grillo Lab centers on revealing how mitochondrial dysfunction alters micronutrient metabolism (e.g. metals, branched chain amino
acids, oxygen, vitamins, etc.) to elicit neurodegeneration in movement disorders and other neurometabolic diseases.