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).
Succinate dehydrogenase (SDH) is a highly conserved protein complex located on the inner mitochondrial membrane where it functions during the Krebs cycle by oxidizing succinate to fumarate (1). This reaction is also important for feeding electrons into the electron transport chain. SDH complex contains four subunits: SDH-A, -B, -C, and -D. Mutation of SDH-A often leads to mitochondrial encephalopathy while mutations to subunits B, C, and D lead to tumors of the head and neck (1).
Caspases are essential mediators of programmed cell death and are needed for both the induction of apoptosis as well as for aiding the degradation of cellular structures. Initiator caspases (such as Caspase-9) sense and respond to various signals including intracellular stress or binding of the death receptor to external ligands. Upon dimerization, initiator caspases gets activated, which follows cleavage of downstream effector caspases for carrying out the apoptotic program.
Caspases are typically known for their role in cell death. However some caspases have recently been investigated for their function during cell proliferation and differentiation. Of these caspase-14 shows a unique expression pattern in the skin and appears to be involved in keratinocyte differentiation. Procaspase-14 is detected in the stratifying epithelium while activated caspase-14 is found only in terminally differentiated keratinocytes (1). Caspase-14 activity is not involved in apoptosis. Instead, caspase-14 is important for keratinization of the epithelium.
There are 3 major autophagy pathways- microautophagy, chaperone-mediated autophagy, and macroautophagy. Macroautophagy is the pathway herein referred to as simply autophagy.
