Abstract: Mitochondria are the central organelles that allow eukaryotic cells to efficiently convert nutrients into energy for cellular functions such as anabolic reactions, movement, and regulation. A reduction in the number of mitochondria or the occurrence of dysfunctional mitochondria leads to serious diseases such as the Leigh syndrome. However, such changes have also been connected to Alzheimer’s disease (AD) and many more diseases of different organ systems and occur during the aging process. Mitochondria are, therefore, the linchpin for the homeostasis of individual cells but also lay the foundation for a healthy, functional organism as a whole. Tissues and organs that consume a lot of energy show a loss of function early on if the mitochondria fail. This includes the brain, but also other organs such as the heart or the intestines, which have to provide high performance or are subject to permanent renewal. The importance of mitochondria for the integrity of neurons of the brain may become clear when looking at the almost altruistic behavior of microglia: a transfer of mitochondria into neurons was observed, for example, when neurons were exposed to α-synuclein or tau, hallmarks of Parkinson’s disease or AD (Scheiblich et al., 2024). By establishing tunneling nanotubes, healthy microglia donated the organelles to affected neurons and rescued them by reducing reactive oxidative species. Mitochondria comprise highly dynamic organelles that adjust their shape, location, and number by processes such as fusion and fission. Thus, local events such as noxae might imprint fast on them to serve actual cellular demands. In this perspective, we will focus on recent research regarding mitochondrial failure in AD and on how novel techniques that allow spatial resolution in analyzing these organelles contribute to widening the knowledge in this regard.