Structural Analysis of Mitochondrial Dynamics-From Cardiomyocytes to Osteoblasts: A Critical Review

Abstract

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

Keywords: bone; fission; fusion; heart; hypoxia; inflammation; mitochondria; ultrastructure.

Figure 1

Transmission electron microscopic images of morphological alterations in mitochondria in human skeletal muscle with mitochondriopathy (a) and human hypertrophic heart (b–f). (a) Partition (arrow) and swollen hypodense mitochondria (star). (b) Swollen mitochondria including cristae dissolution (stars). (c) Concentric cristae (star). (d) Mitochondria including undulated cristae. (e) Cytoplasmic tubules involved in de novo biogenesis (star) (f) Megamitochondrium. Institute of Pathology, Regensburg.

Figure 2

Schematic depiction of mitochondrial fusion and fission focusing on the three main components Opa1, Mfn (fusion), and Drp1 (fission). (Modified according to van der Bliek et al. [38]).

Figure 3

Schematic depiction of the multistep process of mitochondrial division. (1) The Endoplasmatic Reticulum (ER) is present at the mitochondrial division site and preconstricts the mitochondrion. (2) At the preconstricted mitochondria site forms the division complex with its main component Drp1, which further constricts the mitochondrion. (3) After the constriction the mitochondrion divides into two mitochondria and the division machinery disassembles. (Modified according to Tilokani et al. [40]).

Figure 4

Transmission electron microscopy of human cardiomyocytes. (a) Subsarcolemmal Mitochondria (SSM; purple) and Intermyofibrillar Mitochondria (IFM; yellow). (b) Perinuclear Mitochondria (PNM; green). Institute of Pathology, Regensburg.

Figure 5

Influence of Ischemia and Reperfusion (I/R) injury on mitochondria and the consequences for the surrounding cardiac microvascular tissues. (Modified according to Wang et al. [88]).

Figure 6

Hypothetic link between bacterial infections (BI) and hypoxia via AMP-activated kinase (AMPK) and Hypoxia-inducible factor-1-alpha (HIF-1α) pathways, which should be proven experimentally to improve our understanding of the cellular mechanisms in osteomyelitis.