Depletion of mitochondrial methionine adenosyltransferase α1 triggers mitochondrial dysfunction in alcohol-associated liver disease

MATα1 catalyzes the synthesis of S-adenosylmethionine, the principal biological methyl donor. Lower MATα1 activity and mitochondrial dysfunction occur in alcohol-associated liver disease. Besides cytosol and nucleus, MATα1 also targets the mitochondria of hepatocytes to regulate their function. Here, we show that mitochondrial MATα1 is selectively depleted in alcohol-associated liver disease through a mechanism that involves the isomerase PIN1 and the kinase CK2. Alcohol activates CK2, which phosphorylates MATα1 at Ser114 facilitating interaction with PIN1, thereby inhibiting its mitochondrial localization. Blocking PIN1-MATα1 interaction increased mitochondrial MATα1 levels and protected against alcohol-induced mitochondrial dysfunction and fat accumulation. Normally, MATα1 interacts with mitochondrial proteins involved in TCA cycle, oxidative phosphorylation, and fatty acid βoxidation. Preserving mitochondrial MATα1 content correlates with higher methylation and expression of mitochondrial proteins. Our study demonstrates a role of CK2 and PIN1 in reducing mitochondrial MATα1 content leading to mitochondrial dysfunction in alcohol associated liver disease.
https://www.nature.com/articles/s41467-022-28201-2

Popular posts from this blog

Managing Patients Taking Xylazine-Adulterated Opioids in Emergency, Hospital, and Addiction Care Settings

Wednesday, June 14, 2023 .   In response to the rapid escalation in the detection of xylazine in the unregulated drug supply, in April 2023, the White House designated fentanyl contaminated with xylazine an "emerging threat". The National Institute on Drug Abuse (NIDA) Center for the Clinical Trials Network (CCTN) convened health care professionals and federal partners to review current practices in xylazine-related testing, treatment, and wound care to inform evolving best-practices in the field. This convening focused on the most critical areas of concern with the goal of rapidly identifying current practices and a xylazine-opioid research agenda.   https://nida.nih.gov/news-events/meetings-events/2023/06/managing-patients-taking-xylazine-adulterated-opioids-emergency-hospital-addiction-care-settings
Read more

Prescription Drug Misuse and Addiction: Compassionate Care for a Complex Problem

This CME activity provides a practical approach to the management of prescription drug misuse and addiction, including how to use the clinical interview and CURES (California's Prescription Drug Monitoring Program) to identify if a problem exists, and how to intervene once the problem has been identified. Animated didactic videos, interactive slides, and video case scenarios will be used to put these principles into practice with a treatment algorithm. The most compassionate approach to tapering patients down and off the medication they are misusing will also be discussed.   https://edhub.ama-assn.org/stanford-medicine-cme/provider-referrer/14533
Read more

International Overdose Awareness Day, August 31

https://www.cdc.gov/drugoverdose/awareness/ioad.html August 31 marks  International Overdose Awareness Day   (IOAD) , the world’s largest annual campaign to end overdose. It’s a day to: Remember  loved ones who have died from drug overdose and acknowledge the grief of the family and friends left behind. Take action  to encourage support and recovery for everyone impacted by substance use and overdose. End overdose  by spreading awareness of overdose prevention strategies. Hashtags : #IOAD2023 #EndOverdose
Read more