The Upsides and Downsides of Organelle Interconnectivity

Abstract

Interconnectivity and feedback control are hallmarks of biological systems. This includes communication between organelles, which allows them to function and adapt to changing cellular environments. While the specific mechanisms for all communications remain opaque, unraveling the wiring of organelle networks is critical to understand how biological systems are built and why they might collapse, as occurs in aging. A comprehensive understanding of all the routes involved in inter-organelle communication is still lacking but important themes are beginning to emerge, primarily in budding yeast. These routes are reviewed here in the context of sub-system proteostasis and Complex Adaptive Systems theory.

Whole-Cell Scale Dynamic Organization of Lysosomes Revealed by Spatial Statistical Analysis

“…Although this strategy provides important structural and functional benefits, specialized functions of the organelles must be coordinated and integrated for cell physiology (Gottschling and Nyström, 2017). Studies have shown that different organelles interact directly and extensively through mechanisms such as membrane contact (Prinz, 2014) and membrane fusion (Martens and McMahon, 2008).…”

The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK)

“…During ERAD, misfolded protein substrates are recognized by molecular chaperones such as Hsp70 and ubiquitinated by E3 ubiquitin ligases that are ER associated (2,4). After the acquisition of a polyubiquitin tag, the ERAD substrate is retrotranslocated from the ER in an ATP-dependent process that utilizes the AAA-ATPase, Cdc48 (in yeast) or p97 (in mammals).…”

“…_______________________________________ Protein quality control allows cells in all organisms to survive proteotoxic stresses and fine-tune their proteome in response to environmental changes (1). Significant recent work has elucidated in great detail how protein quality control pathways operate in the cytoplasm and in the endoplasmic reticulum (ER) (2)(3)(4). Common to both pathways is the delivery of substrates to the cytoplasmic proteasome, which selectively degrades ubiquitinated and misfolded protein substrates (5).…”

MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

“…Such dynamic responses require a highly coordinated network of processes and signals that are largely compartmentalized to specific organelles and subcellular complexes. To orchestrate the vastly complex cellular system, communication between organelles is paramount . Mitochondria act as a cellular hub that senses and integrates environmental changes, and as a coordinator of adaptive responses through constant communication with other cellular compartments, including the nucleus, regulate key cellular processes that have a significant impact on health span and life span .…”