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.

Nutrient-Dependent Mitochondrial Fission Enhances Osteoblast Function

“…PA-induced lipotoxicity has been associated with mitochondrial fission. [12,27,33,36,37]. In our studies, however, we have found that although the non-lipotoxic 25 µM PA dose induced mitochondrial fission process via activation of DRP1, this process is associated with enhanced mitochondrial respiration and mineralization.…”

Ultrastructural Evidence of Mitochondrial Dysfunction in Osteomyelitis Patients

“…This contradicts the findings of Sasaki and colleagues, who demonstrated that HIF-1 is upregulated in spontaneous wound healing and bone repair in a mouse model resembling osteomyelitis [ 56 ]. Since mitochondrial fission agent dynamin-related protein 1 (DRP1) is interconnected with and induced by HIF-1a [ 8 , 23 , 57 ], the inhibition of mitochondrial fission might offer a comparable target to reduce inflammation and restore bone mineralization. Because of mitochondrial fission’s central role in several cellular pathways, it offers an optimal lever to control the physiology of the cell, both for pathogens and medical agents.…”

“…Due to the obvious direct interconnection between bone cells and infection-causing bacteria, mitochondrial dynamics and function in bone cells following infection have gained increasing attention [ 7 , 8 ]. Mitochondria are responsible not only for energy production, but also for several vital processes such as calcium homeostasis, cellular immunity and even cell death or apoptosis in eukaryotic cells [ 9 ].…”

Calcium Overload and Mitochondrial Metabolism

“…Mitochondrial ultrastructure undergoes dramatic changes during metabolic perturbations or in the presence of certain genetic modifications [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. As such, calcium overload is a way to induce mitochondrial structural modifications.…”