Understanding Mitophagy Mechanisms: Canonical PINK1/Parkin, LC3-Dependent Piecemeal, and LC3-Independent Mitochondrial Derived Vesicles

New Players in the Mitophagy Game

Optogenetic Control of Mitophagy: AMBRA1 based mitophagy switch

Marked for Deletion: Parkin Ubiquitinylates HIF-1α to Stop Cancer

Parkin Ubiquitinylates HIF-1 alpha

By Jamshed Arslan Pharm.D.

There's an autophagy for that!

PINK1 as a Mitochondrial Health Sensor and Neuroprotector

The role of Parkin and autophagy in retinal pigment epithelial cell (RPE) degradation

The root of Parkinson’s disease (PD) points to a poorly regulated electron transport chain leading to mitochondrial damage, where many proteins need to work cohesively to ensure proper function.  The two key players of this pathway are PINK1, also known as PTEN or PARK6, and Parkin, also known as PARK2 - where PINK1 acts as an upstream effector of Parkin to regulate mitochondrial dynamics.  Mitochondria must maintain a healthy equilibrium and do so by undergoing a series of fission and fusion event

Parkin - Role in Mitochondrial Quality Control and Parkinson's Disease

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.

PINK1 - performing mitochondrial quality control and protecting against Parkinson’s disease

PTEN-induced putative kinase 1 (PINK1) is a serine/threonine kinase with important functions in mitochondrial quality control. Together with the Parkin protein, PINK1 is able to regulate the selective degradation of damaged mitochondria through autophagy. Normally PINK1 is imported into the mitochondria where it is targeted for proteolytic cleavage. This cleavage event results in unstable products and is the reason PINK1 is difficult to detect in healthy mitochondria.

PINK1: All work and no fun

The protein PINK1 is a mitochondrial-located serine/threonine kinase (PTK) that maintains organelle function and integrity. It not only protects organelles from cellular stress, but it also uses the selective auto-phagocytosis process for cleaning and clearing cell damage. Exner et al initially reported that, in humans, a PINK1 deficiency is linked to autosomal recessive incidences of both neurodegenerative pathology and Parkinson's Disease (PD) (1).