Mitochondrial Dynamics, Mitophagy and Mitochondrial Spheroids in Drug-Induced Liver Injury

2015 ◽  
pp. 264-291
Livers ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 102-115
Author(s):  
Anup Ramachandran ◽  
David S. Umbaugh ◽  
Hartmut Jaeschke

Mitochondria have been studied for decades from the standpoint of metabolism and ATP generation. However, in recent years mitochondrial dynamics and its influence on bioenergetics and cellular homeostasis is also being appreciated. Mitochondria undergo regular cycles of fusion and fission regulated by various cues including cellular energy requirements and pathophysiological stimuli, and the network of critical proteins and membrane lipids involved in mitochondrial dynamics is being revealed. Hepatocytes are highly metabolic cells which have abundant mitochondria suggesting a biologically relevant role for mitochondrial dynamics in hepatocyte injury and recovery. Here we review information on molecular mediators of mitochondrial dynamics and their alteration in drug-induced liver injury. Based on current information, it is evident that changes in mitochondrial fusion and fission are hallmarks of liver pathophysiology ranging from acetaminophen-induced or cholestatic liver injury to chronic liver diseases. These alterations in mitochondrial dynamics influence multiple related mitochondrial responses such as mitophagy and mitochondrial biogenesis, which are important adaptive responses facilitating liver recovery in several contexts, including drug-induced liver injury. The current focus on characterization of molecular mechanisms of mitochondrial dynamics is of immense relevance to liver pathophysiology and have the potential to provide significant insight into mechanisms of liver recovery and regeneration after injury.


Praxis ◽  
2010 ◽  
Vol 99 (21) ◽  
pp. 1259-1265 ◽  
Author(s):  
Bruggisser ◽  
Terraciano ◽  
Rätz Bravo ◽  
Haschke

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.


Hepatology ◽  
2004 ◽  
Vol 40 (4) ◽  
pp. 773-773 ◽  
Author(s):  
Jay H. Hoofnagle

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
C Agne ◽  
K Rifai ◽  
HH Kreipe ◽  
MP Manns ◽  
F Puls

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
AB Widera ◽  
L Pütter ◽  
S Leserer ◽  
G Campos ◽  
K Rochlitz ◽  
...  

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