Succinate dehydrogenase is an important tetrameric protein involved in the citric acid cycle. It is localized to the inner mitochondrial membrane of cells. Succinate dehydrogenase makes up Complex II of the electron transport chain (ETC) and is responsible for the conversion of succinate to fumarate. This enzymatic reaction also generates a molecule of FADH2, harnessed by the ETC to make energy for the cell. SDHA, the flavoprotein subunit of the succinate dehydrogenase tetrameric complex, interacts with SDHB, SDHC, and SDHD in the complex.
TGF beta (transforming growth factor beta) is a superfamily of cytokines that participate in a variety of cellular processes including growth, proliferation, differentiation, and apoptosis. There are 3 classes of receptors for TGF beta cytokines and they are known as type I, II, and III. TGF beta receptor type III (TGF beta-RIII) is a high affinity receptor for TGF beta-I and TGF beta-II and binds other TGF beta ligands with lower affinities. It is a 250-300 kDa protein that can exist as a single pass transmembrane protein or in its soluble/secreted form.
Actin is the widely studied and ubiquitous cytoskeletal protein capable of forming dynamic microfilament structures. These filaments are essential for diverse cellular functions including cell shape, migration, cytokinesis, and intracellular trafficking (1). Actin is present in three main isoforms: alpha, beta, and gamma. These globular actin isoforms (G-actin) assemble into dynamic filamentous polymers called F-actin. This process is highly regulated by various actin-binding proteins that affect the stability, organization, and depolymerization of F-actin (1).
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that controls the expression of a diverse set of genes. In the absence of ligand, AHR is retained in the cytoplasm. Upon ligand binding AHR translocates to the nucleus where it forms a heterodimer with aryl hydrocarbon receptor nuclear translocator (ARNT) (1). This receptor complex then recognizes AHR-response elements in target genes to regulate their transcription.
Parkin/PARK2 is a cytosolic enzyme which gets recruited to cellular mitochondria damaged through depolarization, ROS or unfolded proteins accumulation, and exert protective effects by inducing mitophagy (mitochondrial autophagy). Parkin induces mitophagy by promoting mitofission (mitochondrial division) and by ubiquitinating mitochondrial proteins to facilitate their recognition/recruitment to the autophagosomal surface.
YAP1 (Yes-associated protein 1) is a transcriptional co-activator which acts as a major effector of Hippo signaling pathway that regulates organ size/ tissue homeostasis and cell proliferation, and is an established oncogene (1). Hippo signaling activation results in the phosphorylation mediated inactivation of YAP1, and restriction of YAP1’s transcriptional activity is the principal mechanism of growth and tumor suppression by Hippo pathway.
Apoptosis, also called programmed cell death, is an essential process in development and disease. The signaling networks that carry out apoptosis is consists of a series of endoproteases called caspases which are synthesized as inactive zymogens. Caspses are grouped into two classes: initiator caspases and effector caspases. Initiator caspases are activated by the assembly of multi-protein complexes such as the death-inducing signaling complex (DISC) (1).
Caspase-7 is an effector caspase with important roles in mediating cell death signaling. As an effector caspase, caspase-7 is cleaved and activated by initiator caspases such as caspase-1 (1). Like other caspase family proteins, caspase-7 contains a catalytic cysteine residue in its active site. This allows caspase-7 to cleave various substrates, such as PARP, to aid in the degradation and destruction of the cell (2).
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor (PRR) that plays an important role in recognizing bacterial pathogens and initiating an immune response. As a PRR, NOD2 recognizes bacterial lipopolysaccharide (LPS), muramyldipeptide (MDP), and other pathogen-associated molecular patterns (PAMPs). NOD2 is a 110 kDa cytoplasmic protein belonging to the Nod-like receptor (NLR) family. Its expression is largely restricted to monocytes and other antigen-presenting cells (APCs).
