AMPK and Autophagy

The cellular recycling process of autophagy appears to be important in many of the known methods of slowing aging through manipulation of metabolism. AMPK is a protein involved in the control of metabolism that is important and of interest in aging research, and this may be because of its influence over autophagy: researchers "have discovered how AMPK, a metabolic master switch that springs into gear when cells run low on energy, revs up a cellular recycling program to free up essential molecular building blocks in times of need. ... AMPK activates a cellular recycling process known as autophagy by activating an enzyme known as ATG1, that jumpstarts the process. The newly uncovered direct molecular connection between AMPK and ATG1 is significant because dysfunctions in both AMPK signaling and autophagy are implicated in a plethora of aging-related diseases, including type II diabetes, cancer, and neurodegenerative diseases such Parkinson's and Alzheimers. ... the group focused on large intracellular structures called mitochondria, whose role is to generate energy. ... Mitochondria are easily damaged in detoxifying tissues like liver. A critical way that defective mitochondria are turned over is through a special form of autophagy called mitophagy. ... In that case, cells would envelope their unhealthy mitochondria in a membrane, dump them in a cellular acid pit, and recycle the remains. If AMPK initiated the process, cells genetically engineered to lack AMPK might show altered mitochondrial turnover compared to normal cells. And that is precisely what the researchers saw: liver cells in which AMPK had been eliminated contained too many mitochondria, many of which looked spindly, indicating they were moribund, and confirming that AMPK was directing autophagic waste disposal."


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