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

Abstract

Cardiac tissue contains discrete pools of mitochondria that are characterized by their subcellular spatial arrangement. Subsarcolemmal mitochondria (SSM) exist below the cell membrane, interfibrillar mitochondria (IFM) reside in rows between the myofibrils, and perinuclear mitochondria are situated at the nuclear poles. Microstructural imaging of heart tissue coupled with the development of differential isolation techniques designed to sequentially separate spatially distinct mitochondrial subpopulations have revealed differences in morphological features including shape, absolute size, and internal cristae arrangement. These findings have been complemented by functional studies indicating differences in biochemical parameters and, potentially, functional roles for the ATP generated, based upon subcellular location. Consequently, mitochondrial subpopulations appear to be influenced differently during cardiac pathologies including ischemia/reperfusion, heart failure, aging, exercise, and diabetes mellitus. These influences may be the result of specific structural and functional disparities between mitochondrial subpopulations such that the stress elicited by a given cardiac insult differentially impacts subcellular locales and the mitochondria contained within. The goal of this review is to highlight some of the inherent structural and functional differences that exist between spatially distinct cardiac mitochondrial subpopulations as well as provide an overview of the differential impact of various cardiac pathologies on spatially distinct mitochondrial subpopulations. As an outcome, we will instill a basis for incorporating subcellular spatial location when evaluating the impact of cardiac pathologies on the mitochondrion. Incorporation of subcellular spatial location may offer the greatest potential for delineating the influence of cardiac pathology on this critical organelle.

Fig. 1.

A: longitudinal ultrathin (70 nm) electron microscopy sections from left ventricular mouse heart imaged at ×6,000. B: longitudinal ultrathin (70 nm) electron microscopy sections from left ventricular mouse heart imaged at ×10,000. The bar equals 0.5 μm. SSM, subsarcolemmal mitochondria; IFM, interfibrillar mitochondria.

Fig. 2.

Z-series fluorescent images of Mitotracker (633 nm laser at 2.0% power, LP 650 nm emission filter) and 4′,6-diamidino-2-phenylindole (405 nm laser at 6.1% power, BP 420–480 nm filter) stained adult mouse cardiomyocytes, which were collected sequentially through the entire cell. Three different focal planes from the center of the cell are shown. Images were acquired on a Zeiss LSM510 confocal with a 63×/1.40 Oil DIC Plan-Apochromat objective at 1.7× zoom.