Independent and sensory human mitochondrial functions reflecting symbiotic evolution

Abstract

The bacterial origin of mitochondria has been a widely accepted as an event that occurred about 1.45 billion years ago and endowed cells with internal energy producing organelle. Thus, mitochondria have traditionally been viewed as subcellular organelle as any other - fully functionally dependent on the cell it is a part of. However, recent studies have given us evidence that mitochondria are more functionally independent than other organelles, as they can function outside the cells, engage in complex "social" interactions, and communicate with each other as well as other cellular components, bacteria and viruses. Furthermore, mitochondria move, assemble and organize upon sensing different environmental cues, using a process akin to bacterial quorum sensing. Therefore, taking all these lines of evidence into account we hypothesize that mitochondria need to be viewed and studied from a perspective of a more functionally independent entity. This view of mitochondria may lead to new insights into their biological function, and inform new strategies for treatment of disease associated with mitochondrial dysfunction.

Keywords: SARS-CoV-2; exosomes; independent mitochondria; mitochondria; sensory mitochondria; sentinel mitochondria; tunneling nanotubes; virus.

Figure 1

Mitochondrial multidirectional informational sharing. Mitochondria can share information in a multidirectional manner among themselves, as well as with bacteria, viruses and a eukaryotic host cell. This exchange of information is facilitated by the use of the “shared biochemical language” evolving simultaneously.

Figure 2

Dynamic nature of mitochondria. Mitochondria are dynamic entities that exhibit multiple kinds of motion in response to external cues and intracellular environment. For example, if a region of the cell becomes disrupted, healthy mitochondria can migrate to that area. Mitochondria also travel between cells, using exo- and endo-cytosis pathways, and extracellular mitochondria have independence to move through extracellular space, for example, to reach compromised areas in the case of cerebral ischemia, hypoxia, etc. (Hayakawa et al., 2016). There are two primary mechanisms through which mitochondria can traffic between cells: they can enter into membrane-enclosed vesicles called exosomes that are secreted by the cell, which also contain mtDNA; or they can travel through cellular tunneling nanotubes. Recently it has also been suggested that mitochondria and their products can make use of gap junction channels for intercellular transfer. This mobility demonstrates that mitochondria are not bound to the cell in which they were formed, and may serve as mobile emergency battery (energy) and sensory units (see text).