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Advances into Understanding the Vital Role of the Mitochondrial Citrate Carrier (CIC) in Metabolic Diseases

The mitochondrial citrate carrier (CIC) is a nuclear-encoded protein located in the inner mitochondrial membrane. By mediating efflux of citrate from the mitochondria to the cytosol, CIC links mitochondrial central carbon metabolism and cytosolic lipogenesis together. Abnormal activity or expression of CIC was found in cancers, developmental disorders and many other diseases. Recently, the specific inhibitors of CIC were proved to modify basic cellular metabolism, which in turn led to changes in disease course such as reverted steatohepatitis and cancer cell death. CIC is believed to be a key player and may serve as a novel therapeutic target in types of human metabolic diseases. Therefore, in this paper, we integrally described the structure and function of CIC. Then, we gave an overview of CIC related diseases including cancers, congenital diseases, pro-inflammatory effects and some other diseases. At the same time, the potential molecular mechanisms of CIC in the above diseases were illuminated. Finally, we illuminated some emerging areas for future investigation.

 

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Title: The Mitochondrial Citrate Carrier (CIC): Structure, Function, and Implications in Human Metabolic Diseases

Abstract: The mitochondrial citrate carrier (CIC) is a nuclear-encoded protein located in the inner mitochondrial membrane. Its role in mediating the efflux of citrate from the mitochondria to the cytosol establishes a crucial link between mitochondrial central carbon metabolism and cytosolic lipogenesis. Aberrant activity or expression of CIC has been identified in various diseases, including cancers, developmental disorders, and metabolic disorders. Recent studies have demonstrated that specific inhibitors targeting CIC can modulate cellular metabolism, resulting in favorable changes in disease progression, such as reversed steatohepatitis and cancer cell death. Given its significance, CIC represents a promising therapeutic target for a range of human metabolic diseases. This paper provides a comprehensive review of the structure and function of CIC, an overview of CIC-related diseases encompassing cancers, congenital disorders, pro-inflammatory effects, and other conditions. Additionally, the potential molecular mechanisms underlying the involvement of CIC in these diseases are elucidated. Finally, emerging areas for future investigation pertaining to CIC are highlighted.

Keywords: mitochondrial citrate carrier, CIC, metabolic diseases, lipogenesis, cancer, congenital disorders, pro-inflammatory effects, therapeutic target.

1. Introduction
   1.1 Mitochondrial citrate carrier (CIC) and its role in cellular metabolism
   1.2 Significance of CIC in human metabolic diseases

2. Structure and Function of CIC
   2.1 Molecular structure and localization of CIC
   2.2 Transport mechanism of citrate across the mitochondrial membrane
   2.3 Regulation of CIC activity and expression

3. CIC-Related Diseases
   3.1 CIC in cancer development and progression
   3.2 Congenital diseases associated with CIC dysfunction
   3.3 Pro-inflammatory effects of abnormal CIC activity
   3.4 Other diseases linked to CIC abnormalities

4. Molecular Mechanisms of CIC in Disease
   4.1 Altered lipogenesis and its impact on disease pathogenesis
   4.2 Dysregulated energy metabolism and its consequences
   4.3 Influence of CIC on cellular redox balance and oxidative stress
   4.4 Other molecular pathways involving CIC in disease development

5. Therapeutic Potential of Targeting CIC
   5.1 Current approaches to modulating CIC activity
   5.2 Preclinical and clinical evidence for CIC-targeted therapies
   5.3 Challenges and future directions for CIC-based therapeutic interventions

6. Conclusion
   6.1 Recapitulation of CIC's role in human metabolic diseases
   6.2 Potential impact of CIC-targeted therapies
   6.3 Prospects for further investigation and translational research in CIC biology

By providing a comprehensive understanding of the structure, function, and disease associations of CIC, this paper aims to shed light on the potential of CIC as a novel therapeutic target in various human metabolic diseases. The insights gained from this research may pave the way for the development of innovative treatment strategies and the improvement of patient outcomes in the future.

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Cat.No. Product Name Information
S2968 CTPI-2 CTPI-2 is an inhibitor of mitochondrial citrate carrier SLC25A1 with KD of 3.5 μM. CTPI-2 is a unique regulator of glycolysis that limits the metabolic plasticity of cancer stem cells (CSCs).

Related Targets

Mitochondrial Metabolism