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Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increasing evidence suggests that mtDNA mutations, mtDNA epigenetics and miRNA regulations dynamically modify signalling pathways in an altered microenvironment, resulting in cancer initiation and progression and aberrant therapy response. In this review, we discuss mitochondria as organelles importantly involved in tumorigenesis and anti-cancer therapy response. Tumour treatment unresponsiveness still represents a serious drawback in current drug therapies. Therefore, studying aspects related to genetic and epigenetic control of mitochondria can open a new field for understanding cancer therapy response. The urgency of finding new therapeutic regimens with better treatment outcomes underlines the targeting of mitochondria as a suitable candidate with new therapeutic potential. Understanding the role of mitochondria and their regulation in cancer development, progression and treatment is essential for the development of new safe and effective mitochondria-based therapeutic regimens.<\/jats:p>","DOI":"10.3390\/ijms23147897","type":"journal-article","created":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T03:41:33Z","timestamp":1658115693000},"page":"7897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential"],"prefix":"10.3390","volume":"23","author":[{"given":"Alexandra","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia"},{"name":"Department of Simulation and Virtual Medical Education, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-3510","authenticated-orcid":false,"given":"Helena","family":"Kosnacova","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia"},{"name":"Department of Simulation and Virtual Medical Education, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-5084","authenticated-orcid":false,"given":"Miroslav","family":"Chovanec","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Jurkovicova","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"ref_1","first-page":"1016","article-title":"Revisiting the hallmarks of cancer","volume":"7","author":"Fouad","year":"2017","journal-title":"Am. 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