Alzheimer’s Disease, Mitochondria, and the Role of Microproteins with Dr. Miller

Join us for an enlightening episode featuring Dr. Miller, who shares his research focusing on the impact of mitochondrial DNA variants, particularly mitochondrial SNP rs2853499, on Alzheimer's Disease (AD), neuroimaging, and transcriptomics.Dr. Miller's team successfully mapped this SNP to a new mitochondrial small open reading frame called SHMOOSE, which has the potential to encode a microprotein. For the first time ever, they have detected two unique SHMOOSE-derived peptide fragments in mitochondria using mass spectrometry, marking an exciting breakthrough in the detection of mitochondrial-encoded microproteins.We delve into how levels of SHMOOSE in human cerebrospinal fluid (CSF) correlate with age, CSF tau, and brain white matter volume, providing crucial insight into the potential role of this microprotein in the onset and progression of AD.Dr. Miller also discusses the results of functional experiments his team conducted. These revealed that SHMOOSE acted on the brain following intracerebroventricular administration, influenced mitochondrial gene expression in multiple models, localized to mitochondria, bound the inner mitochondrial membrane protein mitofilin, and enhanced mitochondrial oxygen consumption.In this episode, listeners will gain a comprehensive understanding of Dr. Miller's groundbreaking work and its profound implications for the fields of neurobiology, Alzheimer’s disease, and microproteins.Keywords: Alzheimer's Disease, Mitochondria, Microproteins, Mitochondrial DNA variants, SHMOOSE, Neuroimaging, Transcriptomics, Mitofilin, Neurobiology.Miller, B., et al. Mitochondrial DNA variation in Alzheimer’s disease reveals a unique microprotein called SHMOOSE. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01769-3