Mitochondrial biogenesis in cardiac pathophysiology

Abstract

Cardiac performance depends on a fine balance between the work the heart has to perform to satisfy the needs of the body and the energy that it is able to produce. Thus, energy production by oxidative metabolism, the main energy source of the cardiac muscle, has to be strictly regulated to adapt to cardiac work. Mitochondrial biogenesis is the mechanism responsible for mitochondrial component synthesis and assembly. This process controls mitochondrial content and thus correlates with energy production that, in turn, sustains cardiac contractility. Mitochondrial biogenesis should be finely controlled to match cardiac growth and cardiac work. When the heart is subjected to an increase in work in response to physiological and pathological challenges, it adapts by increasing its mass and expressing a new genetic program. In response to physiological stimuli such as endurance training, mitochondrial biogenesis seems to follow a program involving increased cardiac mass. But in the context of pathological hypertrophy, the modifications of this mechanism remain unclear. What appears clear is that mitochondrial biogenesis is altered in heart failure, and the imbalance between cardiac work demand and energy production represents a major factor in the development of heart failure.

Persistent disruption of mitochondrial homeostasis after acute kidney injury

“…Initiation of mitochondrial biogenesis occurs in acute injury models (26,27,36,41). We assessed expression of several known mediators of mitochondrial biogenesis by PCR and immunoblot analysis.…”

“…However, the role of mitochondrial fission and fusion following initial injury and during the recovery and maintenance phase is still not completely understood. Mitochondrial biogenesis is initiated after acute organ injuries (27,41), including cellular models of AKI (26). There is an immediate induction of the transcriptional co-activator peroxisome proliferator-activated receptor ␥ co-activator 1-␣ (PGC-1␣) in experimental models of stroke, liver damage, heart failure, and neuromuscular disorders in response to the increased energy demand in such tissues (27,36,38,41).…”

“…Mitochondrial biogenesis is initiated after acute organ injuries (27,41), including cellular models of AKI (26). There is an immediate induction of the transcriptional co-activator peroxisome proliferator-activated receptor ␥ co-activator 1-␣ (PGC-1␣) in experimental models of stroke, liver damage, heart failure, and neuromuscular disorders in response to the increased energy demand in such tissues (27,36,38,41). PGC-1␣ is a primary regulator of mitochondrial biogenesis and is known to associate with transcription factors responsible for mitochondrial gene expression, including the nuclear respiratory factors (NRFs) and mitochondrial transcription factor A (Tfam) (40).…”

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…Sirtuins are class III histone deacetylating enzymes supplied by AMPK with the adequate level of the NAD + , essential activator of Sirt1 that in turn deacetylates PGC-1 and activates its gene expression [75]. Sirt1 is also an important in vivo regulator of mitophagy by deacetylation of the autophagy genes Atg5, Atg7 and Atg8 [134], linking this protective mechanism, devoted to the clearance of depotentiated mitochondria, with PGC-1a mediated biogenesis. For biogenesis to occur it is necessary mitochondria undergo the processes of fusion and fission regulated respectively by mitofusins (Mfn1-2) and by dynamin-related protein(DRP1 and OPA1) [126].…”

Untitled

“…Îäíàê çá³ëüøåííÿ ñêîðîòëèâî¿ àêòèâíîñò³ ì³îêàðäà ó òðåíî-âàíèõ îðãàí³çì³â ìîaeëèâå ëèøå çà óìîâ éîãî åíåðãåòè÷íîãî çàáåçïå÷åííÿ. Òàêà çá³ëüøåíà ïîòðåáà êë³òèí ì³îêàðäà â åíåð㳿 â è ð ³ ø ó º ò ü ñ ÿ ÿ ê â í à ñ ë ³ ä î ê ñ ò è ì óë ÿ ö ³ ¿ ðîçìíîaeåííÿ ì³òîõîíäð³é [29], òàê ³ á³ëüø åôåêòèâíîãî ñèíòåçó àäåíîçèíòðèôîñôàòó (ÀÒÔ). Âêàçàí³ çì³íè ôóíêö³¿ ì³òîõîíäð³é â îñíîâíîìó çóìîâëåí³ çäàòí³ñòþ òîãî ae îêñèäó àçîòó, ùî ñèíòåçóºòüñÿ â êë³òèíàõ ì³îêàðäà, ïðèãí³÷óâàòè â³äêðèâàííÿ ì³òî-õîíäð³àëüíèõ ïîð [7,14,15,32] ³ ïîêðà-ùóâàòè ôóíêö³þ ì³òîõîíäð³é.…”