From lamellar and storage bodies to mitophagy: a comprehensive view of mitochondrial ultrastructure in differentiated SH-SY5Y cells.

Differentiated human SH-SY5Y neuroblastoma cells used to model neurodegenerative defects, cholinergic neuron differentiation, neurotropic virus infection, and neurotoxicity have not been comprehensively studied with fine structure. Our goal is thus to further disclose their cytology. Differentiated in vitro with retinoic acid (RA), SH-SY5Y cells were processed for fine structure analyses with transmission, scanning electron microscopy, and X-ray spectroscopy microanalysis. The neoplastic cells showed typical high nucleus: cytoplasm ratio with neuron-like profiles extending to one long neurite that can carry dense core vesicles and associated cytoskeletons. Among the organelles, one-fifth of mitochondria profiles were noted to bear prominent anomalies of both outer and internal membranes. These organelles formed bursts, long or folded lamellae, with the matrix either replaced by accumulated contrasted compound or striated content created through random sectioning sorts of appendages constituting views of so-called "lamellar bodies," and other dense bodies accompanied by mitophagy. Most lining membranes joined the endoplasmic reticulum network with lipid storage droplets. RA differentiation of neuroblastoma cells involved cell genome and mitochondria metabolism to favor an increased lipid and phospholipids precursors to store associated endoplasm and mitochondria membrane and matrix changes resulting in defective fine structures and content. Some of them bore analogy with those noted when one or more mitochondria regulatory proteins (e.g. OPA1 and mitofusin) occurred in other neurodegenerative pathologies, including Parkinson's disease. Our observations should incite further molecular investigations about this neuroblastoma cell proteome and lipidome organelles because of this cell line usage in numerous biomedical investigations.