Organelles Do Not Exist Alone: A Bidirectional Partnership Across Membranes

Organelles are specialized subcellular structures in eukaryotic cells. Encapsulated by membranes, different organelles perform mutually exclusive biological processes. Organelles communicate actively through vesicular transport pathways and membrane contact sites (MCSs) to maintain cellular homeostasis, allowing the exchange of metabolites and other signals essential for normal cell physiology.

Organelle interactions occur among multiple organelles, including the endoplasmic reticulum (ER), mitochondria, Golgi apparatus, peroxisomes, lipid droplets (LDs), endosomes, and lysosomes. Imbalanced organelle interactions may contribute to various pathological processes. Increasing evidence indicates that abnormal organelle communication promotes cellular senescence and is associated with organ aging.

Endoplasmic Reticulum (ER): Plays a vital role in the synthesis, folding, modification, structural maturation, and targeted deployment of the cellular proteome, and serves as a central hub for lipid metabolism.

Mitochondria: The master regulator of energy metabolism. It has a double membrane system and its own circular genome, known as mitochondrial DNA (mtDNA).

Golgi Apparatus: A central membrane-bound organelle near the nucleus responsible for the transport, processing, and sorting of membrane proteins, secreted proteins, and lipids.

Peroxisomes: Exhibit diverse functions in different cells, including fatty acid β-oxidation, hydrogen peroxide degradation, glycerol metabolism, and maintenance of cellular integrity.

Lipid Droplets: Store neutral lipids for energy or membrane synthesis, mainly located in the cytoplasm.

There are two types of endosomes: early and late. Early endosomes: Cargo generated by the uptake of extracellular materials from the plasma membrane (PM) can be transported to the PM, ER, or late endosomes. Late endosomes: Enter lysosomes via direct acidification or fusion with existing lysosomes.

Lysosomes: Digest extracellular or cell-surface cargo via endocytosis, or degrade intracellular components via autophagy. Both endosomes and lysosomes play critical roles in endocytosis and degradation, forming the endolysosomal system.

1. Core Interaction Network: ER-Centered Organelle Communication

Antibodies for ER-Centered Organelle Interaction Network

2. Mitochondria-Driven Secondary Interaction Network

Antibodies for Mitochondria-Driven Secondary Interaction Network

3. Other Key Interactions

1. Peroxisome-Lysosome: Syt7-PI(4,5)P2 mediates cholesterol transport; defects cause abnormal intracellular cholesterol distribution.

2. Peroxisome-Lipid Droplet: Rab18-NRZ-SNARE and Spastin-ABCD1 mediate fatty acid β-oxidation and protect against lipotoxicity.

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