Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria

Abstract

Schwarzer M, Schrepper A, Amorim P, Osterholt M, Doenst T. Pressure overload differentially affects respiratory capacity in interfibrillar and subsarcolemmal mitochondria. Years ago a debate arose as to whether two functionally different mitochondrial subpopulations, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), exist in heart muscle. Nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function, whereas IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction for 20 wk or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analyzed by electron microscopy. Mitochondria were isolated by differential centrifugation, and respiratory capacity was analyzed using a Clark electrode. Pressure overload induced left ventricular hypertrophy with increased posterior wall diameter and impaired contractile function. Mitochondrial state 3 respiration in control was 50% higher in IFM than in SSM. Pressure overload significantly impaired respiratory rates in both IFM and SSM, but in SSM to a lower extent. As a result, there were no differences between SSM and IFM after 20 wk of pressure overload. Pressure overload reduced total citrate synthase activity, suggesting reduced total mitochondrial content. Electron microscopy revealed normal morphology of mitochondria but reduced total mitochondrial volume density. In conclusion, IFM show greater respiratory capacity in the healthy rat heart and a greater depression of respiratory capacity by pressure overload than SSM. The differences in respiratory capacity of cardiac IFM and SSM in healthy hearts are eliminated with pressure overload-induced heart failure. The strong effect of pressure overload on IFM together with the simultaneous appearance of mitochondrial and contractile dysfunction may support the notion of IFM primarily producing ATP for contractile function. heart failure; mitochondrial population; mitochondrial respiration; pressure overload MITOCHONDRIA SERVE AS the primary site for substrate oxidation and ATP generation and are essential for cell and contractile function. Based on location, two distinct populations of cardiac mitochondria have been distinguished: interfibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM) (34). It has been a matter of debate whether these populations are also functionally different. The Hoppel group described differences in their biochemical and respiratory properties (34) and ultrastructure (37). In contrast, McKean (30) suggested that cardiac

Xanthine oxidase inhibition preserves left ventricular systolic but not diastolic function in cardiac volume overload

“…Most studies have reported the effects of cardiac hypertrophy associated with VO or pressure overload on subpopulations of mitochondria. It is of interest that interfibrillar mitochondria show a greater respiratory capacity than subsarcolem- mal mitochondria in healthy Spague-Dawley rat hearts but have greater depression of respiratory capacity and LV contractile dysfunction after 20 wk of pressure overload (35). The use of the Seahorse extracellular flux analyzer provides the ability to localize the metabolic changes to intact cardiomyocytes excluding contamination from multiple cells types, maintaining mitochondrial localization in the cell, and obviating damage to mitochondria during isolation (14,16,32).…”

Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

“…These authors reported a reduced capacity for free radical scavenging that was specific for SSM. In contrast, rats that underwent transverse aortic constriction for 20 wk displayed decreased total mitochondrial content, as well as decreased state 3 and state 4 respiration rates, which impacted IFM to a greater extent (115). It is unclear as to why the results differ, but it may be related to the differences in pathological model used and/or animal model of choice.…”

Rol de la función mitocondrial en el corazón y sus implicaciones en disfunciones cardíacas

“…Producción de ATP para los procesos de contracción y relajación [28], [29]. Estructura Redondas con crestas más compactas (lameliformes) [18], [30].…”

“…Velocidad de consumo de oxígeno durante la síntesis de ATP Alta (miocardio de perro y humano) [22], [23]. Alta (miocardio de roedores) [21], [31], [32] 4 Disfunción cardíaca asociada a mitocondrias disfuncionales…”

“…Por el contrario, las SSM preservaron la actividad de CPT1 y utilizaron eficiente el palmitato como sustrato. Schwarzer et al [32], evaluaron las SSM e IFM de corazón de rata macho que presentaron hipertrofia ventricular inducida, en el estudio, los autores encontraron una reducción en el estado respiratorio 3 para las IFM, junto con la aparición de disfunción contráctil en el corazón. Con base a las evidencias obtenidas en el estudio, se soporta la idea de que las IFM producen el ATP principalmente para la función contráctil.…”