The speaker at the final plenary session was by Beth Levine of the University of Texas Southwestern. She gave the State of the Art lecture. She was engaging speaker with clear slides. This wasn’t her first rodeo.

She began with brief history and definition of autophagy, a cellular process that uses lysosomes to digest metabolize and recycle old and damaged organelles. It was first described in a rodent kidney in 1957. Christian de Duve was awarded the 1974 Nobel Prize in Medicine for discovering lysosomes. She stated that the field took off with the discovery of the a set of evolutionarily conserved genes that regulated the process.

Autophagy = selective lysosomal degradation pw to get rid of things that are too large to be degraded by ubiquitin pw | Levine #kidneywk14

— Nature Reviews Nephrology (@NatRevNeph) November 16, 2014

Dr. Levine showed data that blocking autophagy in various tissues of the kidney results in kidney disease including nephrotic syndrome, kidney failure, and obstruction.

Autophagy has roles in ageing, cancer, ER stress, aspects of innate/adaptive immunity says Beth Levine #kidneywk14

— Nature Reviews Nephrology (@NatRevNeph) November 16, 2014

One of the key players in autophagy is the protein Beclin-1, discovered in the 1990’s.

She then started to show her work on exercise.

Exercise is good for you. Known since Plato. Mechanism is unclear. #kidneywk14

— Joel M. Topf, MD FACP (@kidney_boy) November 16, 2014

We know that autolysis is unregulated in response to stress, so she was interested in what happens in response to exercise.

Increasing exercise causes increased autophagosomes #kidneywk14

— Joel M. Topf, MD FACP (@kidney_boy) November 16, 2014

While investigating why autophagosomes are increased with exercise they discovered a second protein BCL-2, which inhibits autophagy by interacting with Beclin-1. Stress (exercise) disrupts the complex of Beclin-1 and BCL-2. They have done additional work defining the precise molecular mechanism by which this happens. By removing BCL-2 there is increased autophagy and healthier cells.

By blocking removal of BCL-2 in a custom mouse they were able to make a mouse that could not get benefit of exercise #kidneywk14

— Joel M. Topf, MD FACP (@kidney_boy) November 16, 2014

She even had a video of mice with modified BCL-2 that got really tired on a treadmill compared to wild type.

Mice that can’t turn on autophagy show deficient exercise endurance, caused by inability to increase insulin sensitivity #kidneywk14

— Nature Reviews Nephrology (@NatRevNeph) November 16, 2014

She went on to discuss work in diabetic mouse models and explained that diabetogenic diets are neutralized by exercise, but if you block the disassociation of BCL-2 and Beclin-1 the diabetogenic diet induces insulin resistance.

She then shifted gears and explored autophagy’s role in infectious diseases and ischemic disease.

Therapeutic autophagy-inducing peptide can inhibit pathogenic replication (eg. HIV) and prevent lethal infection (eg. WNV) #kidneywk14

— Nature Reviews Nephrology (@NatRevNeph) November 16, 2014

Their small peptide that induces autophagy needs to be used carefully. At high doses it induced a unique form of cell death called autosis. This cell death is regulated by Na/K-ATPase and her lab is exploring blocking it with cardiac glycosides.

Autosis can be induced by autophagy-inducing peptide, by starvation and by neonatal cerebral hypoxia-Ischemia #kidneywk14

— Nature Reviews Nephrology (@NatRevNeph) November 16, 2014

Cardiac glycosides may be protective against autosis via blocking Na-K-ATPase, protective in ischemic models. #kidneywk14

— Joel M. Topf, MD FACP (@kidney_boy) November 16, 2014

Cardiac glycoside treatment to inhibit autosis is protective in renal I/R reperfusion injury model: reduced fibrosis #kidneywk14

— Nature Reviews Nephrology (@NatRevNeph) November 16, 2014

The talk was great and lived up to the billing of a State of the Art lecture. It is wonderful to see science break into the simplest forms of health like exercise and find processes that could be used to treat diseases as diverse as diabetes and West Nile Virus.

Post written by Dr. Joel Topf,  eAJKD Advisory Board member.

Check out more of eAJKD’s coverage of Kidney Week 2014! Also, follow @eAJKD on Twitter for live updates!