Davide D’Amico: Mitochondrial autophagy

We associate getting older with a loss of energy. On the molecular level, this is quite literally true, because one of the hallmarks of aging is mitochondrial dysfunction. Mitochondria are often referred to as “the powerhouse of the cell,” because they convert nutrients from the food we eat into usable energy, in the form of ATP. But as we age, mitochondria become less effective at generating the energy we need for various chemical processes.

So why does this happen? As with most things in biology, there are definitely multiple factors at work here. But one likely reason is a failure of quality control. As we age, mitochondrial autophagy (aka mitophagy) declines, and our body starts to accumulate broken and dysfunctional mitochondria. This becomes most obvious in tissues that consume a lot of energy, like skeletal muscle. Hence, mitochondrial dysfunction is linked to poor muscular strength in older people. If we could find a way to ramp up mitophagy, perhaps we could retain excellent mitochondrial function throughout our golden years.

In this episode of humanOS Radio, Dan Pardi welcomes Dr. Davide D’Amico to the show. Davide is a research scientist in the field of metabolism and aging. He was previously a post-doc at the Auwerx Laboratory of Integrative Systems Physiology at the École Polytechnique Fédérale de Lausanne (EPFL), where he investigated the role of mitochondrial function in health, disease, and the aging process.

PINK1: Mitochondrial quality control

PINK1 is the cell’s surveillance system for damaged mitochondria. An unusual kinase, it only stabilizes in the presence of a depolarized mitochondrion; once stabilized, it activates a mitophagy pathway that leads to clearance of the damaged organelle.

PINK1 activation has been shown to oppose the inflammation, mtDNA mutations, and metabolic/proteostatic failures that can lead to cell death in disease.

LEARN MORE: Mitokinin

Mitophagy

Mitophagy in cellular homeostasis

Pathogenic protein species implicated in neurodegenerative diseases (e.g., alpha synuclein, beta amyloid, tau, and TDP43) can associate with mitochondria and drive mitochondrial dysfunction.

Mitophagy, the process by which cells clear their damaged mitochondria, plays an important protective role in these circumstances: not only is the normal, healthy mitochondrial pool restored, but the proteotoxic species are cleared along with the bad mitochondria.

Mitokinin’s scientists have shown that by potentiating the PINK1 pathway in times of proteotoxic stress, neuron health can be restored and disease-driving pathologies reduced or eliminated.

LEARN MORE: Mitokinin

CohBar Mitochondrial-derived Peptides

CohBar is a clinical stage biotechnology company focused on the research and development of mitochondria based therapeutics. Mitochondria based therapeutics originate from the discovery by CohBar’s founders of a novel group of naturally occurring mitochondrial-derived peptides within the mitochondrial genome that regulate metabolism and cell death, and whose biological activity declines with age.

To date, the company has discovered more than 100 mitochondrial derived peptides and generated over 1,000 analogs. CohBar’s efforts focus on the development of these peptides into therapeutics that offer the potential to address a broad range of diseases.