PNAS: shocked! Does retinal cell and cancer cell height resemble unexpectedly?

February 24, 2019 / Bio Valley - how much does a healthy retinal cell look like a tumor cell? It hijacks a chemical reaction of production capacity to mass produce the molecular components needed When tumor cells do this, they use these molecular elements to promote their own growth and metastasis But when retinal cells do this, they renew the photoreceptor membrane in the eye to maintain our visual acuity Photo source: Jianhai Du, a scientist at the University of West Virginia (WVU), PNAs, is analyzing how the retina does this His latest discovery was recently published in PNAS "We eat glucose and use it as a major source of energy." Du said he is an associate professor in the Department of Biochemistry and the Department of Ophthalmology and Visual Sciences at WVU medical college Through multi-step chemical reaction, any cell in our body can convert glucose into energy material, and the mitochondria in the cell will burn it into energy Only less than 20% of glucose is used to produce new cell materials "But in tumor cells, it's almost the opposite." Du said Tumor cells change the way they react, converting most of the glucose into the basic components of the tumor "It's like they're building different houses When you build a house, you need basic materials like wood and cement When a tumor grows, it needs membranes, lipids, and nucleotides " Retinal cells also use glucose in a similar way, but not to maintain tumor growth and metastasis They use these materials to produce new photoreceptor outer membrane, which is used to replace the old damaged membrane Du and his team suspect that a protein called mitochondrial pyruvate carrier 1 (mpc1) plays a key role in this process Mpc1 is essential for the transport of glucose derivative pyruvate to mitochondria, which is then burned for capacity But in cancer cells, mpc1 levels are reduced because the cells do not want pyruvate to enter the mitochondria The researchers used animal models to study whether and how mpc1 is related to retinal health They also tested whether a small amount of pyruvate entering the mitochondria of the retina was important The team knocked out all mpc1 in some of their animal models, while the rest remained intact "We found that a small amount of glucose being used by mitochondria is important for mitochondrial function, photoreceptor function and viability." Du said The researchers also found severe visual impairment in animal models with mpc1 deficiency Compared with the mpc1 model, their photoreceptors function is less than half of the former The team also found that knockout of mpc1 can lead to retinal degeneration In addition, it can damage the structure of mitochondria in retina in a very unique way "An important factor in age-related macular degeneration is the inability of mitochondria to function properly But people don't know what is causing this phenomenon, and there is no effective therapy to treat it at present " Du said Du's research may give a glimmer of light to the emergence of the disease and how doctors can treat it He and his colleagues are conducting experiments to determine whether fat can also be used as an energy substitute for the mitochondria of the retina that do not normally use glucose References: Allison Grenell et al Loss of MPC1 reprograms retinal metabolism to impair visual function, Proceedings of the National Academy of Science (2019) Doi: 10.1073/pnas 1812941116