Post-translational modifications and protein quality control of mitochondrial channels and transporters

Mitochondria play a critical role in energy metabolism and signal transduction, which is tightly regulated by proteins, metabolites, and ion fluxes. Metabolites and ion homeostasis are mainly mediated by channels and transporters present on mitochondrial membranes. Mitochondria comprise two distinct compartments, the outer mitochondrial membrane (OMM) and the inner mitochondrial membrane (IMM), which have differing permeabilities to ions and metabolites. The OMM is semipermeable due to the presence of non-selective molecular pores, while the IMM is highly selective and impermeable due to the presence of specialized channels and transporters which regulate ion and metabolite fluxes. These channels and transporters are modulated by various post-translational modifications (PTMs), including phosphorylation, oxidative modifications, ions, and metabolites binding, glycosylation, acetylation, and others. Additionally, the mitochondrial protein quality control (MPQC) system plays a crucial role in ensuring efficient molecular flux through the mitochondrial membranes by selectively removing mistargeted or defective proteins. Inefficient functioning of the transporters and channels in mitochondria can disrupt cellular homeostasis, leading to the onset of various pathological conditions. In this review, we provide a comprehensive overview of the current understanding of mitochondrial channels and transporters in terms of their functions, PTMs, and quality control mechanisms

DESIGNING THOUGHTFUL EXPERIENCES FOR KIDS ON VOICE ASSISTANTS

ABSTRACT Voice Assistants (VAs) have become commonplace in households, and in countries with average or higher penetration rate of VAs, kids born over the last decade have grown up being familiar with these VAs. However, experiences for kids on VAs have advantages as well as disadvantages. This paper provides an overview of how VAs work, what’s unique to the user segment of kids, and what these pros and cons of letting kids interact with VAs are. Finally, it also provides guidelines to craft thoughtful experiences for kids on voice assistants. Keywords: Artificial Intelligence, ASR, Human Computer Interaction, NLP, NLU, Voice Technology. Cite this Article: Ashlesha Vishnu Kadam, Designing Thoughtful Experiences for Kids on Voice Assistants, International Journal of Artificial Intelligence & Machine Learning (IJAIML), 2(1), 2023, pp. 75-81

Neuronal loss of NCLX-dependent mitochondrial calcium efflux mediates age-associated cognitive decline

Summary: Mitochondrial calcium overload contributes to neurodegenerative disease development and progression. We recently reported that loss of the mitochondrial sodium/calcium exchanger (NCLX), the primary mechanism of mCa2+ efflux, promotes mCa2+ overload, metabolic derangement, redox stress, and cognitive decline in models of Alzheimer’s disease (AD). However, whether disrupted mCa2+ signaling contributes to neuronal pathology and cognitive decline independent of pre-existing amyloid or tau pathology remains unknown. Here, we generated mice with neuronal deletion of the mitochondrial sodium/calcium exchanger (NCLX, Slc8b1 gene), and evaluated age-associated changes in cognitive function and neuropathology. Neuronal loss of NCLX resulted in an age-dependent decline in spatial and cued recall memory, moderate amyloid deposition, mild tau pathology, synaptic remodeling, and indications of cell death. These results demonstrate that loss of NCLX-dependent mCa2+ efflux alone is sufficient to induce an Alzheimer’s disease-like pathology and highlights the promise of therapies targeting mCa2+ exchange