For decades, scientists have puzzled over how ATP, our body's main source of energy, moves into the endoplasmic reticulum (ER). Recently, researchers made a groundbreaking discovery: the transporter protein SLC35B1 is the key to unlocking…
Secrets of Cellular Energy: The ER’s ATP Transporter
Cells are the fundamental building blocks of life, and each one requires a constant supply of energy to function. This energy comes primarily in the form of adenosine triphosphate (ATP), often called the cell’s energy currency. While the mitochondria are well-known for producing ATP, other cellular components also need it. One crucial player is the endoplasmic reticulum (ER), a vital organelle involved in protein production and processing. But the ER lacks its own ATP production mechanism. So, how does it get its energy? Scientists have recently made a breakthrough, identifying the key ATP transporter responsible for delivering this vital energy molecule.
The Mystery of ER ATP Import
For years, scientists puzzled over how the ER received its essential ATP supply. Several potential transporters were proposed and subsequently ruled out. However, recent research strongly implicates SLC35B1, also known as AXER (ATP/ADP exchanger in the ER membrane), as the primary transporter responsible for shuttling ATP into the ER lumen. This discovery is a significant step forward in understanding cellular energy dynamics.
SLC35B1: The Key Player
SLC35B1 belongs to a family of nucleotide sugar transporters (NSTs), primarily known for transporting sugar molecules into the ER and Golgi apparatus. Surprisingly, this protein also efficiently transports ATP. Studies using RNA interference (RNAi) techniques demonstrated that reducing SLC35B1 levels significantly lowered ATP levels within the ER, confirming its critical role in ATP import.
Confirming the Role of SLC35B1
Further research employed various techniques to solidify the role of SLC35B1. Thermal shift assays, which measure protein stability in the presence of different molecules, revealed that ATP and ADP bind strongly to SLC35B1, increasing its resistance to heat denaturation. Saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy provided further evidence by directly detecting the interaction between ATP and ADP with SLC35B1. In addition, researchers also conducted transport assays using reconstituted SLC35B1 in artificial cell membranes. These experiments demonstrated that SLC35B1 facilitates the exchange of ATP and ADP across the ER membrane, confirming its function as an ATP/ADP exchanger.
Structural Insights
Scientists also determined the three-dimensional structure of SLC35B1 using cryo-electron microscopy (cryo-EM). This structure revealed that SLC35B1 indeed adopts a drug–metabolite transporter (DMT) fold, a common structural motif in membrane transport proteins. Understanding its structure further elucidates how this transporter works at the molecular level.
The Process Behind Protein Folding
Why is Protein Folding Important?
Protein folding refers to how proteins take on their functional shape or structure within cells. Each protein must fold properly to work effectively; otherwise, problems can arise. The chaperone proteins like Hsp70 use ATP to help proteins fold correctly within the ER while also helping them get rid of misfolded proteins through a process called degradation.
Further Implications
The discovery of SLC35B1’s role in the ER ATP transporter has broad implications for our understanding of cellular function and disease. The ER plays a critical role in protein folding and quality control. Consequently, disruptions in ER ATP levels can affect many cellular processes and contribute to various diseases. This research opens exciting avenues for investigating these diseases and developing novel therapeutic strategies.
Reference
- Gulati, A., Ahn, D., Suades, A., Hult, Y., Wolf, G., Iwata, S., Superti-Furga, G., Nomura, N., & Drew, D. (2025). Stepwise ATP translocation into the endoplasmic reticulum by human SLC35B1. Nature. https://doi.org/10.1038/s41586-025-09069-w
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Neha Adikane holds a Master’s degree in Environmental Science from Pune University, bringing a unique blend of scientific expertise and creative writing skills to her craft. She specializes in creating engaging, insightful, and impactful content across various niches. With a passion for translating complex ideas into simple, relatable narratives, she excels at crafting blogs, articles, website content, and social media posts that captivate readers and drive engagement. Neha’s background in environmental science adds depth to her writing, allowing her to effectively cover topics related to sustainability, eco-awareness, and scientific innovations.
