Mechanisms of Nonvesicular Ceramide Transport

Abstract

Ceramides, as key components of cellular membranes, play essential roles in various cellular processes, including apoptosis, cell proliferation, and cell signaling. Ceramides are the precursors of all complex sphingolipids in eukaryotic cells. They are synthesized in the endoplasmic reticulum and are further processed at the Golgi apparatus. Therefore, ceramides have to be transported between these two organelles. In mammalian cells, the ceramide transfer protein forms a contact site between the ER and the trans-Golgi region and transports ceramide utilizing its steroidogenic acute regulatory protein-related lipid transfer domain. In yeast, multiple mechanisms of nonvesicular ceramide transport have been described. This involves the nuclear–vacuolar junction protein Nvj2, the yeast tricalbin proteins, and the lipocalin-like protein Svf1. This review aims to provide a comprehensive overview of nonvesicular ceramide transport mechanisms and their relevance in cellular physiology. We will highlight the physiological and pathological consequences of perturbations in nonvesicular ceramide transport and discuss future challenges in identifying and analyzing ceramide transfer proteins.

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“…One of these processes involves the synthesis of ceramides in the ER, which are a family of lipid molecules that are transferred to the GA for subsequent conversion into complex sphingolipids [3]. This transfer can occur Cells 2024, 13, 316 2 of 22 through vesicular transport or direct contact between these organelles [4]. Regardless of the inter-organelle communication mechanism, proteins serve as primary mediators of functional interactions between different organelles, and an increasing number of proteins participate in these processes, categorized by their functions as structural, recruitment, regulatory, and anchoring proteins, among others [5].…”