Healthcare (Commonwealth Union) – The negative perception surrounding the “cholesterol” is quite immense. Clogged arteries, heart attacks and strokes are often what come to mind for most people. However, in the world of healthcare good cholesterol known as high-density lipoprotein (HDL) and bad cholesterol known as low-density lipoprotein (LDL) have a distinctly different impact on our health.
When it comes to the microscopic world of human cells, cholesterol plays a very different role, serving as a vital component that helps keep cells functioning and alive.
A study led by Nanyang Technological University, Singapore’s (NTU Singapore) Lee Kong Chian School of Medicine (LKCMedicine), has revealed how cells quickly transport cholesterol to their “recycling centres,” known as lysosomes. This process helps strengthen the lysosomes and prevents them from rupturing as they break down damaged or obsolete cellular components.
Published this month in Nature Communications, the research offers new insights into how this cellular recycling system may become impaired in age-related neurological conditions, including Parkinson’s and Alzheimer’s diseases.
Every moment, tiny structures within our cells known as mitochondria act as microscopic power plants, producing the energy needed to keep life going. But over time, these cellular powerhouses can become damaged and deteriorate. If they are not removed, harmful fragments released from dysfunctional mitochondria can contribute to cell death.
Cells have a specialised quality-control process to deal with this problem, known as mitophagy. During this process, damaged mitochondria are enclosed and transported to lysosomes — highly acidic compartments that function as the cell’s recycling centres. Lysosomal enzymes then dismantle the worn-out mitochondria, allowing their components to be recycled and reused.
Although researchers have understood the broad workings of mitophagy for years, an important question has remained unanswered: How do lysosomes preserve their highly acidic conditions and withstand the physical stress involved in breaking down such large cellular cargo without rupturing?
A new study has now identified an unexpected part of the answer: cholesterol.
The co-first authors, who are NTU Research Fellows Dr Yang Haoning and Dr Koji Matsuhisa, made use of advanced live-cell imaging methods and monitored the molecular occurrences within living cells like never before.
Many scientists in various fields have pointed to link of mitochondrial damage to a wide variety of conditions, hence putting the need for mitochondria to be under greater spot light by researchers. Researchers of the study indicated that when damaged mitochondria are sent to lysosome the PI4KIIα enzyme forms the PI4P lipid responsible for signaling which tags the lysosomal membrane.
The corresponding author Associate Professor Yasunori Saheki, Irene Tan Liang Kheng Chair Professor in Neuroscience at LKCMedicine, indicated that lysosomes are required to be kept in an extremely acidic interior for the digestion of cellular waste in a proper manner. they found that as lysosomes absorb damaged mitochondria, they shore up their membranes with cholesterol. This procedure assists in maintaining the lysosome resiliance and makes sure that its digestive functions are kept active.
The scientist’s evaluation showed another intriguing finding as well. When the lysosome was able to digest the mitochondrial membranes, it sent out a strong increase of lipids that are called free fatty acids. If they remain free in the cell, the fatty acids may get toxic.
To resolve this issue the cell utilizes a series of enzymes to put these fatty acids into safe storage units known as lipid droplets. This method changes toxic waste into energy storage for its utilization in future.
“By mapping how lipid transfer protects lysosomes during mitochondrial damage, we open up potential new therapeutic targets aimed at preserving cellular health during aging” explained LKCMedicine Research Fellow Dr Yang Haoning.
