Fundamental roles for inter-organelle communication in aging

Abstract

Advances in public health have nearly doubled life expectancy over the last century, but this demographic shift has also changed the landscape of human illness. Today, chronic and age-dependent diseases dominate the leading causes of morbidity and mortality worldwide. Targeting the underlying molecular, genetic and cell biological drivers of the aging process itself appears to be an increasingly viable strategy for developing therapeutics against these diseases of aging. Towards this end, one of the most exciting developments in cell biology over the last decade is the explosion of research into organelle contact sites and related mechanisms of inter-organelle communication. Identification of the molecular mediators of inter-organelle tethering and signaling is now allowing the field to investigate the consequences of aberrant organelle interactions, which frequently seem to correlate with age-onset pathophysiology. This review introduces the major cellular roles for inter-organelle interactions, including the regulation of organelle morphology, the transfer of ions, lipids and other metabolites, and the formation of hubs for nutrient and stress signaling. We explore how these interactions are disrupted in aging and present findings that modulation of inter-organelle communication is a promising avenue for promoting longevity. Through this review, we propose that the maintenance of inter-organelle interactions is a pillar of healthy aging. Learning how to target the cellular mechanisms for sensing and controlling inter-organelle communication is a key next hurdle for geroscience.

Organellomics: AI-driven deep organellar phenotyping of human neurons

“…The relevance of organellomics studies root from the intricate network of organellar interactions, which allows cells to regulate compartment content and functions (Cohen, Valm, and Lippincott-Schwartz 2018; Donahue, Ruark, and Burkewitz 2022; Rossini, Pizzo, and Filadi 2021; Schrader, Kamoshita, and Islinger 2020). This is not limited to membrane-bound organelles, as the intricate cellular communication network extends to encompass interactions of membrane-bound and membraneless organelles (Bussi et al 2023; Amen and Kaganovich 2021; Liao et al 2019; Qin et al 2023) and between different membraneless organelles (Stoecklin and Kedersha 2013).…”

The endoplasmic reticulum connects to the nucleus by constricted junctions that mature after open mitosis in mammalian cells

“…The two types of ER–NE junctions we observed – with and without a luminal connection – raise the possibility that ER–NE junctions can change configuration. The membrane contact sites between the ER and other organelles such as mitochondria, endosome, and plasma membrane respond to various environmental cues including nutrient stress, ER stress and calcium stimulation (Donahue et al, 2022; Jang et al, 2022). Similarly, the membrane junctions between the ER and the NE might change their morphology in response to environmental stimuli.…”